No retraction, correction or concern found when last checked on Oct 23, 2026.

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

Amina Ait-Ammar, Anna Kula, Gilles Darcis and 7 more

Frontiers in Microbiology · 2020 · Review · CC BY

doi:10.3389/fmicb.2019.03060

Abstract

One of the most explored therapeutic approach aiming at eradicating the HIV-1 reservoirs is the “shock and kill” strategy which is based on HIV-1 reactivation in latently-infected cells (“shock” phase), while maintaining ART in order to prevent spreading of the infection by the neosynthesized virus. This kind of strategy would allow the “kill” phase during which latently-infected cells would then die from viral cytopathic effects or from host cytolytic effector mechanisms following viral reactivation. Several latency reversing agents (LRAs) with distinct mechanistic classes have been characterized to reactivate HIV-1 viral gene expression. Some LRAs have been tested in terms of their potential to purge latent HIV-1 in vivo in clinical trials, showing that reversing HIV-1 latency is possible. However, LRAs alone have failed to reduce the size of the viral reservoirs. Together with the inability of the immune system to clear the LRA-activated reservoirs and the lack of specificity of these LRAs, the heterogeneity of the reservoirs largely contributes to the limited success of clinical trials using LRAs. Indeed, HIV-1 latency is established in numerous cell types that are characterized by distinct phenotypes and metabolic properties, and these are influenced by patient history. Hence, the silencing mechanisms of HIV-1 gene expression in these cellular and tissue reservoirs need to be better understood to rationally improve this cure strategy and hopefully reach clinical success.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 23, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

1Approximately, 36.9 million people in the world are living with HIV, while there were 33.3 million in 2010, showing that HIV is still a global public health problem (UNAIDS 2018).

2The development of ART has allowed the suppression of virus replication to undetectable levels. Thus, ART reduces HIV-associated morbidity, prolongs survival, prevents transmission, and results in a partial reconstitution of the immune system, as measured by an increase in circulating CD4+ T cells. However, ART can cause cumulative toxic effects with the emergence of HIV-1 drug-resistant variants. Moreover, ART is unable to achieve complete virus eradication since it targets only actively replicating virus, and as such, treatment needs to be taken life-long. The main barrier to an HIV cure is the formation of stable reservoirs of latent HIV-1 that are defined as a cell type or an anatomical site in which integrated proviruses persist. The latent reservoirs are highly heterogeneous and composed of multiple cell types, such as macrophages, but the best-characterized ones are a small population of HIV-1-infected memory CD4+ T cells. In addition to cellular reservoirs, GALT, CNS, genital tract, and lymph nodes are the main anatomical reservoirs of HIV-1. The role of the respiratory tract, liver, kidney, and adipose tissue as HIV-1 reservoirs is also gaining importance. Moreover, an anatomical site in which ART penetration is limited (called a sanctuary) or a site which is immune-privileged (such as B cell follicular centers within lymph nodes, testis, and the brain) may allow for residual replication contributing to viral persistence. Together, these reservoirs can be induced to actively produce viruses by various cellular stimuli and therefore represent one potential source of rebound of viremia after ART interruption.

3Viruses have developed different mechanisms to escape the host immune system. In addition to the rapid evolution of viral variants, the establishment of viral latency in the infected cells is one of these mechanisms. Latently-infected cells contain stably-integrated, replication-competent proviruses repressed by a plethora of silencing mechanisms operating at the transcriptional and post-transcriptional levels. The number of latently-infected cells carrying replication-competent proviruses is extremely low with a majority of defective proviruses. Significant progress has been made in the development of various therapeutic approaches that target HIV-1 and prevent disease progression. Currently, two strategies are under investigation in order to reach long-term control of viral replication in the absence of ART: the first strategy is aiming at achieving a sterilizing cure (i.e., a total elimination of the virus from the human body), whereas the second is a functional cure (i.e., a remission or long-term control of HIV-1 in the absence of ART, without loss of CD4+ T cells, no clinical progression, lack of HIV-1 transmission, and a reduction of the size of the reservoirs). Given the difficulty of achieving a sterilizing cure, one specific approach for a functional cure, called the “shock and kill” strategy, has become one of the major focus of attention. However, it now appears that the main barrier to reaching success with this “shock and kill” strategy is the heterogeneity of the latent HIV-1 reservoirs that is reflected by the diversity of infected cell types residing in the blood and in the different tissues and by the complexity of the molecular mechanisms governing latency and most likely differing from one cell to the other.

4The present review will discuss the heterogeneity of the HIV-1 reservoirs that has been highlighted by studies using LRAs. We will describe the determinants responsible for these heterogeneous responses to LRAs, including the diversity of cell types composing the reservoirs (their origin, their differentiation, and their activation state). We will briefly present the multiple molecular mechanisms governing latency, the HIV-1 diversity within the latent and reactivated reservoirs, the patient-to-patient and cellular variations in response to LRAs. Finally, we will discuss why a better understanding of these elements is crucial for reaching an HIV-cure.

CD4+ T Cell Reservoirs

5HIV-1 infects subsets of CD4+ T lymphocytes, leading either to productively-infected cells or, rarely, to latently-infected cells. HIV-1 infected CD4+ T cells can be distinguished either by their state of differentiation, by their function, or by the markers they express on their surface.

CD4+ T Cell Differentiation Subsets

6CD4+ T cells infected with HIV-1 can be grouped by their state of differentiation into naive T cells (TN, CD45RA+, CD62L+, and CD95–) and memory CD4+ T cells, which can be further divided into four subpopulations: central memory T cells (TCM, CD45RA–, CCR7+, and CD27+), effector memory T cells (TEM, CD45RA–, CCR7–, and CD27–), transitional memory T cells (TTM, CD45RA–, CCR7–, and CD27+), and stem cell-like memory T cells (TSCM, CD45RA+, CCR7+, CD27+, and CD95+). TN cells that are more resistant to HIV-1 infection than memory CD4+ T cells and as such contain lower levels of HIV-1 DNA, produce as many virions or greater amount of replication-competent HIV-1 than the memory CD4+ T cells following latency reversal with LRAs, indicating that TN cells are an important reservoir of latent HIV-1. Moreover, the total proportion of TN increases under ART regimen compared to memory T cells. However, clonal expansion is more frequently observed in memory than in TN cells, thus contributing to HIV-1 persistence. Indeed, homeostatic proliferation driving clonal expansion has been evidenced by pioneering work of that identified TCM and TTM as the main reservoir for HIV-1 infection. These two major subgroups are a more stable reservoir for HIV-1 than TEM which are short-lived and, unlike TCM and TTM, express markers of activation (HLA-DR) and might be more sensitive to programmed cell death. It has been previously shown by the group of Sarah Palmer that TEM which are in an activation state carry the highest number of intact proviruses compared to TCM, TTM, and TN. This finding suggests that the resting phenotype of CD4+ T cells (i.e., characterized by no expression of activation markers) is not a prerequisite for latent infection. These differences could be explained by patient-specific variations related to the duration of infection before ART initiation or to the duration of ART. Moreover, some evidence supports the theory that HIV-1 can establish latent infection in actively replicating CD4+ T cells, suggesting that HIV-1 infection of both resting and activated primary CD4+ T cells could result in latency. The TTD, corresponding to aged T-cell populations that reflect HIV-1 disease progression and in which integrated HIV-1 DNA is also detected, are a very small reservoir with a reduced frequency in HIV-1 individuals under suppressive ART and improved CD4+ T cell counts. Finally, TSCM are permissive to HIV-1 infection and contribute to its persistence by their capacity of self-renewal and prolonged survival rate. The proportion of viral DNA associated with these TSCM cells is higher than in TCM. Although TSCM are latently-infected, they represent only a small fraction of the total reservoir.

CD4+ T Cell Functional Subsets

7Different CD4+ T cell subsets that are generated from TN were shown to be HIV-1 infected. For instance, resting CD4+CD25+ Treg were found to be sensitive to HIV-1 infection acting as a viral reservoir in patients under long ART. These cells are characterized by a lesser response to T cell activation which limits virus expression and inhibits CD8+ T-cell cytotoxic function. Additionally, the gamma-delta T cells (γδ T) which represent approximately 2 to 10% of total circulating CD3+ T lymphocytes and whose majority express TCR from Vδ2 variable regions (hereafter referred as Vδ2 cells), are classified as memory cells according to the expression of CD45RO and CD27 markers. These Vδ2 cells have been documented to be productively infected and depleted upon HIV-1 infection. More recently, it has been demonstrated that Vδ2 cells in ART-treated patients with complete suppression of HIV-1 plasma viremia harbor latent HIV-1 that can replicate following ex vivo stimulation indicating that peripheral Vδ2 T cells are a potential HIV-1 reservoir. Also, Th17 CCR6+ memory CD4+ T-cell subsets in the blood and colon are long-lived cells that act as HIV-1 reservoirs during ART. In addition, T follicular helper cells (Tfh) from the germinal center and peripheral blood (pTfh) are highly susceptible to HIV-1 infection holding replication-competent virus and serve as reservoirs during ART. These cells are characterized by surface expression of CXCR5 and PD-1, reside in the lymph node follicles in immediate anatomical proximity to B cells, and support the germinal center reaction essential for the generation of effective humoral immunity. Notably, the group of Matthieu Perreau, by investigating lymph node Tfh (expressing CXCR5 and PD-1) and pTfh (expressing CXCR3), has shown that these subpopulations are the major sources of infectious replication-competent HIV-1.

8Very recently, resident memory CD4+ T cells (TRM), present in tissues such as the lower female genital tract has been described as a critical HIV-1 reservoir in cervical mucosa. Interestingly, cervical tissues from aviremic ART-treated HIV-1 infected woman contained higher viral DNA content compared to blood samples and showed that CD4+ TRM harboring viral DNA and viral RNA are the main contributors to this reservoir.

Markers of Latently-Infected CD4+ T Cells

9Studies investigating the role in latency of activation markers such as HLA-DR and immune checkpoint molecules (i.e., PD-1, LAG-3, TIGIT and Tim-3) have indicated that these markers are preferentially expressed at the surface of memory CD4+ T cells (TCM and TTM) harboring latent HIV-1 provirus. Although several studies, including those carried on SIV-infected macaques, have demonstrated that cells expressing these markers carry latent, replication-competent integrated viral DNA, the replication competence of the integrated proviruses and the contribution of the cells bearing these markers to the latent reservoir still need to be fully elucidated.

10Recently, the expression of CD32a has been reported as a potential marker of memory CD4+ T cells harboring a replication-competent latent virus in aviremic patients under ART. The role of CD32a as a cellular marker of HIV-1 reservoirs has been the subject of several works. A complete study presented at CROI by Darcis et al. (CROI 2019, Poster 346 - CD32+ CD4+ T cells are enriched in HIV-1 DNA) showed that active CD4+ T cells co-expressing HLA-DR and CD32a are highly enriched with HIV-1 DNA.

11The integrin α4β7 has been shown on a T cell subset that is highly susceptible to HIV-1 infection. Moreover, the integrin α4β1 was shown to be expressed by more than 70% of infected cells both in untreated and ART-suppressed individuals. Integrins mediate the adhesion and transendothelial migration of lymphocytes facilitating their homing to GALT (for α4β7) and to the inflamed central nervous system/bone marrow (for α4β1) suggesting a role in HIV-1 persistence by enhancing T cell expansion.

12In addition, high levels of CD2 receptor expression on latently infected resting memory CD4+ T cells in virally suppressed HIV-1-infected subjects has been also identified. Moreover, CD30 receptor was identified on transcriptionally active CD4+ lymphocytes in individuals on suppressive ART suggesting that it might be a marker of residual, transcriptionally active HIV-1 infected cells in the setting of suppressive ART. Last but not least, very recently the B lymphocyte antigen CD20 has also been identified as a marker of transcriptionally-active HIV-infected cells.

Non-T Cell Reservoirs

13Even though memory CD4+ T cells are a long-term cellular reservoir for HIV-1, they are not the only source of viral rebound during treatment interruption. Macrophages, DCs, and tissue macrophages, such as microglial cells, are part of the viral reservoir.

14Indeed, overwhelming evidence supports the notion that tissues, such as the CNS, lymph nodes, testes, gut, genital tract, and lungs, serve as HIV-1 sanctuaries that counteract viral eradication. In this regard, the group of Morgane Bomsel has recently reported that urethral tissue macrophages expressing IL-1 receptor, CD206, and IL-4 receptor, but not CD163, constitute a replication-competent HIV-1 reservoir. Importantly, lipopolysaccharides specifically reactivate the production of replication-competent infectious proviruses from these tissue macrophages.

15In the case of circulating monocytes, they are more resistant to HIV-1 infection and their contribution as a viral reservoir is controversial and remains debatable. Monocytes have been proposed as a vehicle of HIV-1 dissemination throughout the body upon their entry in tissues where they differentiate into macrophages. Especially, due to their ability to cross the blood-tissue barrier, monocytes consequently, spread the infection into sanctuaries such as the brain. These characteristics indicated the monocytes as an important viral reservoir. However, even if several studies have reported persistent infection of monocytes in ART treated individuals, others failed to detect HIV-1 in circulating monocytes. A recent work from the group of Nicolas Chomont indicated that monocyte infection is infrequent, and they highlighted the importance of using flow cytometry cell-sorting to minimize contamination by CD4+ T cells.

16Follicular dendritic cells (fDCs) in lymphoid tissues specialized in the trapping and retention of antigens in the form of immune complexes on their surface, including HIV-1 virions, can serve as a potential viral reservoir. Using specific and sensitive next-generation in situ hybridization approach, documented the importance of B cell follicles in active, latent, and persistent infections by analyzing lymphoid tissues from macaques prior to and during ART. These fDCs could thus transfer the virus to T cells present in the follicles of secondary lymphoid organs. In addition, myeloid dendritic cells (mDCs) located in the lymph nodes may support a very low level of viral replication and have a role in HIV-1 latency. However, the mechanism of viral persistence in these cells is not yet clearly understood [reviewed in ].

17Viral DNA has also been detected in hematopoietic stem cells (HSCs) from ART-treated patients, which could demonstrate their involvement in HIV-1 persistence. Despite the limited infection and detection of HSCs in a subset of patients, their role as a viral reservoir may be crucial. Finally, HIV-1 can infect kidney allografts after transplantation despite undetectable viremia thereby suggesting that podocytes can serve as viral reservoirs and revealing once again the heterogeneous composition of the HIV-1 reservoir.

18In conclusion, multiple cell subsets being present at various cellular differentiation states, either resting or activated, can serve as HIV-1 reservoir. All these cells contribute to the complexity and heterogeneity of the reservoirs of latent HIV-1. It is very likely that different molecular mechanisms of latency establishment and persistence are involved in different latently-infected cell types and even may vary among cells of the same lineage.

Complexity of Molecular Mechanisms Regulating HIV-1 Latency

19It is well established that repression of HIV-1 expression is mediated through a plethora of molecular mechanisms both for the establishment and for the maintenance of post-integration latency (summarized in Figure 1). In fact, HIV-1 latency is a multifactorial phenomenon, controlled by several interlinked mechanisms operating at the transcriptional and post-transcriptional levels [reviewed in )] and influenced by the transcriptional program of the host cell. For instance, some studies have suggested that HIV-1 viral latency is related to the integration site and orientation of the provirus. HIV-1 integration seems random but favors the introns of transcriptionally-active genes located in gene dense regions in the outer shell of the nucleus close to the nuclear pores. The importance of transcriptional interference as a mechanism suppressing the expression of the integrated provirus (including steric hindrance, convergent transcription, and enhancer trapping) has also been proposed [reviewed in ].

20Moreover, during latency, the HIV-1 promoter is heavily controlled by epigenetic mechanisms, including DNA methylation and histone post-translational modifications, such as histone acetylation, methylation, and crotonylation. The degree of DNA methylation on the HIV-1 promoter was long considered controversial due to conflicting observations in patients. However, this heterogeneity in promoter methylation profile between patients has now been explained by the duration of the infection and/or the duration of ART therapy which impacts the accumulation of cytosine methylation on the 5′LTR. Still, the exact mechanisms of this DNA methylation accumulation in the latent reservoir of HIV-1-infected individuals remain unclear.

21Additionally, an antisense transcript originating from the 3′LTR (named the ASP RNA) was recently shown to recruit the PRC2 repressor complex to the HIV-1 5′LTR, increasing the repressive epigenetic mark H3K27me3 while reducing RNAPII occupancy at the viral promoter and promoting the establishment and maintenance of HIV-1 latency at the epigenetic level. An HIV-encoded antisense long non-coding RNA directs the same epigenetic silencing mechanisms by recruiting and guiding chromatin-remodeling complex consisting of proteins such as DNMT3a, EZH2, and HDAC-1 to the viral promoter leading to transcriptional HIV-1 latency.

22HIV-1 latency is also associated with poor availability of transcriptional activating factors including NF-κB, NFAT, and STAT5 due to their cytoplasmic sequestration and with a low expression level of the viral transactivator Tat. The interaction of the cellular transcriptional cofactor CTIP2 with HP1α is involved in the relocation of Tat to transcriptionally inactive regions of the chromatin. However, HIV-1 counteracts CTIP2 mediated-repression by promoting its degradation by the HIV-1 accessory protein Vpr. Another recent finding has revealed that APOBEC3A, the restriction factor that suppresses HIV-1 infection in macrophages, maintains HIV-1 latency by recruiting KAP1 and HP1 inducing repressive histone marks. In addition, the importance of TRIM22, known to inhibit the binding of Sp1 to the 5′LTR promoter and to colocalize with HIV-1 transcriptional repressors TRIM19/PML, contributes to the maintenance of HIV-1 latency.

23During latency and even after transcription initiation, the RNAPII is paused during early elongation, constraining its processivity and resulting in repression of HIV-1 gene expression. RNAPII terminates prematurely and accumulates at specific positions of the HIV-1 promoter that overlap with the position of the repressive nucleosome nuc-1, positioned in the 5′LTR just after the TAR region, inducing a block of transcriptional elongation. This inhibition of HIV-1 transcription elongation is regulated by the binding of negative factors such as NELF and DSIF to the RNAPII and by the limited availability of the cellular transcription factor P-TEFb due to its sequestration by the 7SK snRNP complex. P-TEFb is composed of CyclinT1 and CDK9 and requires the CDK9 Thr-186 phosphorylation for its activity to mediate the phosphorylation of the C-terminal domain of the paused RNAPII antagonizing its negatives factors. The level of CDK9 phosphorylation has been found to be lower in resting CD4+ T cells harboring latent HIV-1. Furthermore, CTIP2 binds to the 7SK snRNP complex to inhibit P-TEFb and HIV-1 transcription in microglial cells.

24Abortive TAR transcripts have been reported even during transcriptional elongation block. In a very elegant manner, the group of Steven Yukl has evidenced that multiple blocks to transcription and even to splicing and export exist in patient cells. They developed a panel of RT-ddPCR assays to measure at the same time different HIV-1 transcripts in patient-derived cells. They quantified the transcripts suggestive of transcriptional interference (U3-U5), initiation (TAR), 5′ elongation (R-U5-pre-Gag), distal transcription (Nef), completion (U3-polyA), and multiple splicing (Tat-Rev). Using blood CD4+ T cells from HIV-1 individuals under ART, they showed a greater block to HIV-1 transcriptional elongation, distal HIV-1 transcription, completion, and multiple splicing than to transcriptional initiation. This transcription profiling approach highlighted the blocks at distinct stages of HIV-1 transcription and splicing (which may be governed by different mechanisms), thereby underlying the heterogeneity of HIV-1 latency in CD4+ T cells.

25The work of and and also of have highlighted the importance of post-transcriptional blocks in HIV-1 latency. Post-transcriptional blocks of the nuclear export of various viral transcripts including unspliced, partially spliced, multiply-spliced, and translation of HIV-1 RNA by miRNAs have also been reported. Interestingly, a recent study from the group of Alessandro Marcello has demonstrated that the expression level of MATR3 and PSF, two known post-transcriptional cofactors of the HIV-1 protein Rev required for Rev-mediated export of RRE-containing HIV-1 RNAs, are poorly expressed in latently-infected patients cells, suggesting a novel post-transcriptional block linked to RNA export. This latter block was reversed by ectopic overexpression of MATR3 which boosted the action of the HDAC inhibitor SAHA in the J-Lat cell line model for HIV-1 latency. These results demonstrated the importance of post-transcriptional blocks, especially at the level of viral RNAs export, that need to be relieved to reach full viral reactivation by LRAs. Similarly, the work of Andrew Mouland and colleagues has demonstrated that UPF-1, a known RNA surveillance protein, acts as a positive post-transcriptional regulator of viral reactivation from latency.

26Additional post-transcriptional mechanisms including the involvement of cellular miRNA and non-coding RNAs in latency have been described. More specifically, the regulation of viral expression and production by miRNAs targeting PCAF and CyclinT1 have been related to latency. Many of these miRNAs involved in this process are expressed in resting cells but are downregulated during T-cell activation. For instance, the lower susceptibility to HIV-1 infection of monocytes in comparison to macrophages has been shown to be correlated with high and low expression of these miRNAs, respectively. Finally, lncRNA called NRON which is strongly expressed in resting CD4+ T cells was shown to be involved in HIV-1 latency by inducing Tat degradation through the proteasome pathway. The combination of SAHA with NRON knockdown significantly reactivates viral production from latently-infected primary CD4+ T cells.

27Altogether, the complexity of the molecular mechanisms underlying HIV-1 latency marks the heterogeneous nature of the HIV-1 reservoirs.

Shock and Kill Strategy to Eliminate the Latent Reservoir

28Mechanistic insights into HIV-1 transcriptional repression during latency have allowed to develop the “shock and kill” strategy. This approach is based on the use of small-size chemical compounds called LRAs which reactivate HIV-1 from latency (the “shock” phase) while maintaining ART in order to prevent new infection events. This kind of strategy would allow the “kill” phase during which latently-infected cells would then die from viral cytopathic effects or host cytolytic effector mechanisms following viral reactivation. Of note, this strategy does not discriminate between replication-competent and defective proviruses. Several classes of LRAs have been developed and studied (reviewed in;; ). These include: PKC agonists, MAPK agonists, CCR5 antagonist, Tat vaccine, SMAC mimetics, inducers of P-TEFb release, activators of Akt pathway, benzotriazole derivatives, epigenetic modifiers (including HDACis, HMTis, and DNMTis), and immunomodulatory LRAs (including TLR agonists, IL-15 agonist and immune checkpoint inhibitors) (summarized in Table 1).

29It has been further demonstrated by several groups, including ours, that targeting a single mechanism might not be efficient enough to reactivate the majority of latent proviruses and that combinations of LRAs acting on several HIV-1 silencing molecular mechanisms are needed to obtain synergistic viral reactivations and achieve a more significant decrease in the size of the reservoirs. Moreover, when LRAs are used in combination, lower concentrations are effective, thereby reducing the toxicity of each LRA. However, even if these LRA combinations reverse latency, they could inhibit multiple CD8+ T cell function [reviewed in ]. Importantly, despite the potent effect of a single LRA and of LRA combinations in vitro and ex vivo, multiple clinical trials have failed to show a decrease in the size of the latent reservoir in vivo. A clear change in plasma HIV-1 RNA with a subsequent decrease in the reservoir size in vivo has been seen only for the immune check point inhibitor nivolumab and for romidepsin (combined with an immunovaccine) but without prolonging time to viral rebound after ART interruption in this latter study. In the case of nivolumab, the study was conducted only on one patient who experienced a drastic and sustained decrease of the HIV-1 reservoir. However, other controversial studies found no consistent changes in the size of the latent reservoir nor in HIV-specific CD8+ T-cell responses in HIV-1-infected individuals treated with anti-PD1 antibodies (including nivolumab). Success to completely eradicate latent viruses with LRAs is hampered by the heterogeneous nature of the latent reservoir and by the diversity of the silencing mechanisms governing latency that make the current “shock and kill” strategy inefficient.

Latency Reversing Agents Highlight the Heterogeneous Nature of the Latent Reservoir

30All studies investigating LRAs have demonstrated the heterogeneous nature of the cellular and tissue reservoirs of latent HIV-1 and their diverse reactivation capacity, highlighting the different determinant responsible for the heterogeneous responses to LRAs. All these studies are summarized in Table 2.

HIV-1 Diversity Within the Latent and Reactivated Reservoirs

31Few studies so far have focused on investigating the contribution of the viral diversity, the compartmentalization, the intact or defective nature of the viral reservoir, and the origin of the rebounding virus in latency reversal. A previous study in patients who initiated ART during acute infection showed that proviral sequences from PBMCs and GALT presented low level of genomic diversity and divergence and remained unchanged after treatment interruption. Moreover, there was no phylogenetic link between the rebounded plasma viral sequences and those from the GALT proviral DNA, indicating that HIV-1 cellular reservoirs in the GALT may be different from those circulating in peripheral blood and might not contribute to the rebounded plasma viremia. Other studies have supported the compartmentalization idea of the viral population in the gut with divergent opinions. Depending on the stage of HIV-1 infection, the diversity of HIV-1 RNA appears lower in patients with early infection versus chronic infection, and thus, compartmentalization is lost during chronic infection. However, other works have supported other conflicting ideas with findings showing absence of compartmentalization of HIV-1 between the gut and blood, providing evidence for cross infection between these two compartments.

32HIV-1 sequence diversity has been reported to be either higher or similar to genital tract compared to blood. Viral compartmentalization between the blood and the male genital tract has been reported by multiple studies including SIV-infected macaques. More recently, patients under suppressive ART exhibited a significant positive correlation between viral diversity and genetic compartmentalization in the blood and testes, but it was attributable to differential frequencies of identical HIV-1 sequences between the two sites. However, there was no evidence of compartmentalization when only unique sequences per sites are considered, suggesting that compartmentalization between blood and testes is linked to clonal expansion.

33HIV-1 phylogenetic analysis of post-mortem CSF, brain, and spleen from HIV-1 patients under ART and presenting dementia symptoms showed that HIV-1 strains from the blood and spleen are different from those in the brain and CSF. A more recent study of env and nef phylogeny on ART suppressed individuals confirmed the presence of considerable viral diversity in the spleen and lymph nodes. However, there is no viral compartmentalization between spleen and PBMCs in SIV-infected and suppressed rhesus macaques.

34The comparison of latent HIV-1 from the blood and lymph node CD4+ T cells from HIV-1 individuals undergoing ART interruption, after TLR9 coadministration with ART, suggests the same frequencies of intact proviruses in the blood and lymph nodes and the fact that CD4+ T cells carrying latent viruses circulate between the blood and lymphoid tissues. However, there is no overlap between latent reservoirs and rebounded virus, thereby supporting the idea that recombinations may play a role in the emergence of the rebounded viremia.

35Time to ART from estimated date of infection as an early ART initiation is associated with less molecular diversity in CSF without impacting HIV-1 DNA provirus compartmentalization in the CNS which occurs very early after infection. In the study of, a higher diversity in PBMCs than in CSF is reported. The compartmentalized HIV-1 RNA in CNS is found to contribute to viral rebound within the CSF in patients undergoing treatment interruption but is phylogenetically distinct from those present in the paired blood plasma.

36Most of the previous studies estimated that blood memory CD4+ T cells are the source of viral rebound after ART interruption or viral reactivation from latency. The first work of Timothy Schacker and colleagues examined HIV-1 variants by single-genome amplification and phylogenetic analyses in matched lymph nodes, GALT biopsies and blood from HIV-1 suppressed individuals under longstanding ART after treatment interruption. The rebounded virus after treatment interruption was found to be detectable in latently-infected cells at multiple sites with a highly complex and genetically diverse population of virions which bring out the challenges facing the heterogeneity of HIV-1 reservoir. Another study of the effect of a brief treatment interruption on the HIV-1 latent reservoir of individuals who initiated ART during chronic infection showed no alteration either in the size or in the diversity of the peripheral reservoir and highlighted the substantial variability and the prevalence of clonally-expanded viral populations. Interestingly, the group of Sarah Palmer indicated that analytical treatment interruption (ATI) activated proviruses with similar sequence between plasma and intestinal lamina propria mononuclear cells, indicating that intestinal HIV-1 reservoir is contributing to viremia following ATI. A recent study by the group of Linos Vandekerckhove confirmed the heterogeneous source of viral rebound from distinct anatomical reservoirs in HIV-1 individuals undergoing treatment interruption, showing that genetically-identical viral expansions play a significant role in viral rebound. In a study presented by Oliveira et al. (CROI 2019, Poster 327—Characterizing the HIV DNA reservoirs in whole-body tissues in the “Last Gift” cohort), HIV-1 DNA was detected in most body tissues with a nice distribution and compartmentalization of HIV-1 reservoir between tissues from the Last Gift cohort enrolling altruistic, terminally-ill persons living with HIV-1. They have successfully sequenced env from 10 different tissues with many identical HIV-env sequences sampled in multiple body tissues.

37Some LRA interventions analyzed whether the increase of CA-US HIV-1 RNA is related to limited or to broad activation of HIV-1 proviruses. The single genome sequencing of viral RNA transcripts showed that panobinostat and vorinostat activate genetically diverse HIV-1 proviruses that are similar to that observed during ATI but with a high percentage of defective viral sequences. More precisely, TCM contributed to the rebounded viremia, indicating once again the important role of this subset in the persistence of latent HIV-1. Finally, romidepsin administration to HIV-1 individuals under suppressive ART activates transcription from blood CD4+ T cells latent HIV-1 proviruses. Importantly, the viremia induced by romidepsin contained few defective mutations and is characterized by low genetic diversity.

38Together, these studies illustrate that cure strategies should consider the complex and variable composition of the different viral reservoirs, the replication-competent capacity, the diversity and compartmentalization of HIV-1 reservoir, and the role of cellular clonal expansion and cellular proliferation in promoting HIV-1 persistence.

Weak Reactivation Potential of Latency Reversing Agents and Post-transcriptional Blocks

39An important issue for the development of a more effective “shock and kill” approach is to determine how effective LRAs are in terms of full viral reactivation from all latently-infected cells composing the reservoirs. Indeed, most of the in vivo reactivation studies demonstrated a rather weak reactivation effect of LRAs, i.e., an effect only on HIV-1 transcription with much less or no effect on plasma HIV-1 RNA. For instance, a recent clinical trial using escalating doses of disulfiram demonstrated that even if all doses produced an increase in the level of intracellular HIV-1 RNA, only the highest dose increased plasma HIV-1 RNA level albeit with very low effect. Similar observations have been reported for SAHA: i.e., weak effect at the level of viral particle production in vivo as assessed by measurement of plasma HIV-1 RNA. have shown in their primary CD4+ T cell models that disulfiram and SAHA treatments increased viral transcription, but failed to effectively enhance viral translation. In addition, the group of Maria Buzon has very recently demonstrated that a median of 16.28% of the whole HIV-reservoir exhibited HIV-1 transcripts induction after viral reactivation using various LRAs and their combinations, but only 10.10% of these HIV-1 RNA+ cells produced viral p24 proteins. Recent work by the group of Andrew Lever has demonstrated that inefficient splicing regulation may also influence the action of LRAs. They studied the polymorphisms occurring in a recently identified viral mRNA splicing regulatory element (ESEtat) regulating tat mRNA splicing which results in more silent phenotypes of the virus. Indeed, higher doses of LRAs (PMA, JQ1, and panobinostat) were required to reactivate silent viruses bearing the polymorphisms in ESEtat, reflecting their lower rate of inducibility as compared to wild-type HIV-1. Therefore, different post-transcriptional mechanisms including blocks to export and alteration of mRNA splicing may be considered as druggable targets for a combined approach of more potent latency reversal.

Cell Model-Specific Effects of Latency Reversing Agents

40Latency reversing agents were shown to be cell model-specific exhibiting diverse reactivation profiles across multiple HIV-1 latency model systems. A comprehensive study by tested the potency of a panel of thirteen LRAs for their ability to reactivate HIV-1 in several broadly used HIV-1 latency models (primary T-cell models, multiple J-Lat cell lines, and ex vivo T-cell cultures derived from the blood of HIV-1+ individuals). They showed that PHA was the only stimulus that uniformly reactivated latent HIV-1 in all these cell models, although other LRAs exerted largely heterogeneous responses among the various models. Importantly, following LRA treatment, none of the in vitro cell model systems could accurately capture the ex vivo response characteristics of latently-infected T cells from patients.

Cell Type-Specific Effects of Latency Reversing Agents

41In addition to cell model-specific effects of LRAs, recent studies demonstrated the cell type-specific effects of LRAs. For instance, highlighted heterogeneous responses of CD4+ populations to bryostatin and ingenol. The authors showed that bryostatin induced HIV-1 expression in TEM cells but had limited effect in TCM and TTM cells. While ingenol, on the other hand, exhibited more similar reactivation effects among the different memory T-cell subpopulations. Similarly, the group of Maria Buzon has very recently demonstrated heterogeneous responses to LRAs of the latent reservoirs present in different CD4+ T-cell subpopulations. Romidepsin and ingenol and their combination were the most potent LRAs at reactivating HIV-1 in almost all the subsets of CD4+ T cells by increasing, respectively, the proportion of TCM, TEM, TTM, TNA, and TNA, TSCM, TCM, TTM cells expressing HIV-1 RNA. Panobinostat successfully reactivated HIV-1 only in TCM cells. Bryostatin-1 reactivated very modestly some T-cell subsets, including TNA, TTD, and TCM. Therefore, T-cell differentiation status may impact the action of LRAs. Indeed, show in ex vivo and in vitro models that differentiated phenotype of TEM cells from that of quiescent TCM cells is associated with a potentiated response to LRAs and to a highest level of inducible HIV-1 reservoir. Additionally, the effects may also be cell type-specific. We have also recently demonstrated that disulfiram exhibited limited reactivation spectra, being active only in myeloid-derived HIV-1 latently infected cell lines (U1, THP89GFP monocytic, and CHME-5/HIV-1 microglial cells) but not in Jurkat-based T-cell lines. These heterogeneous cellular responses to LRAs indicate that distinct and cell-type dependent molecular mechanisms contribute to HIV-1 latency in diverse reservoirs.

Latency Molecular Mechanism-Specific and Tissue-Specific Effects of Latency Reversing Agent

42It has recently been demonstrated by, using an elegant transcriptional profiling approach, that LRAs exhibit silencing mechanisms-specific effects. These authors found that HDACis (panobinostat and romidepsin) and PKC agonists (ingenol 3,20-dibenzoate and ingenol mebutate) exert differential effects on the latency blocks in the blood latently-infected CD4+ T cells. More specifically, HDACis increased total and elongated transcripts but had less or no effect on polyadenylated and multiply spliced transcripts, whereas ingenol mebutate strongly induced polyadenylated and multiply spliced transcripts but had lesser effects on transcription initiation and elongation. These latter results are in agreement with another study showing that romidepsin administration after six doses of the therapeutic vaccine Vacc-4x, in HIV-1 individual under suppressive ART, increased early events in HIV-1 transcription (initiation and elongation) but had less effect on later stages (completion, multiple splicing). The differential effects of these LRAs suggest that the mechanisms underlying the blocks to completion and splicing may differ from those that mediate the blocks to initiation and elongation. The group of Yukl compared CD4+ T cells from the blood and rectum tissue reservoirs using a similar transcriptional profiling approach and found a much greater block to HIV-1 transcription initiation in the rectum compared to blood. Indeed, the ratio of total to elongated transcripts was 6-fold lower in the rectum CD4+ T cells, suggesting less of a block to HIV-1 transcriptional elongation in rectal CD4+ T cells. In fact, a multi-dose trial of SAHA has evidenced that the cell-associated HIV-1 RNA in latently infected CD4+ T cells from the blood was 5-fold higher compared to CD4+ T cells from the rectal tissue, suggesting that the LRA-driven effects may also be tissue-specific. Thus, further studies should investigate whether gut cells differ from blood cells in their response to LRAs in terms of HIV-1 transcript production and of cellular gene expression.

Integration Site-Specific Effects of Latency Reversing Agents

43The group of Guillaume Fillion demonstrated that different LRAs reactivate different subsets of latent proviruses. Using a method called B-HIVE to map the chromosomal locations of individual proviruses, these authors revealed in Jurkat cells that responses to LRAs are also viral integration site-specific. They found that PHA and SAHA reactivated proviruses inserted at distinct genomic locations, suggesting that the insertion context of HIV-1 is a critical determinant of the viral response to LRAs. Using the same B-HIVE technology, the groups of Albert Jordan and Guillaume Fillion demonstrated that MMQO (an LRA which acts as an I-BET) and JQ1 reactivate latent HIV-1 proviruses integrated at distinct sites from those proviruses targeted by SAHA and prostratin. Interestingly, demonstrated that only less than 5% of latently-infected primary CD4+ T cells are reactivated by LRAs. By further sequencing analysis, these authors showed the preference toward integration events in active chromatin sites for the reactivable cell population, while these regions were significantly disfavored in the non-reactivable group, highlighting that the role of chromatin environment is an important determinant of LRA effectiveness.

Patient-Specific and Sex-Specific Effects of Latency Reversing Agents

44Many other determinants may also be responsible for the heterogeneous reactivation profile of LRAs. Patient-dependent effects of LRAs were reported. Indeed, viral productions evident in some patients but not in others were observed in all reactivation clinical trials. Additionally, in our previous reactivation studies, we demonstrated patient-specific variations in terms of reactivation capacity of their ex vivo cell cultures following treatments with various LRAs. Indeed, we established a positive correlation between the size of the HIV-1 reservoirs and the ex vivo capacity of HIV-1-infected patients’ cell cultures to be reactivated by LRAs, but we identified HIV-1+ patients who deviated from this linearity relative to their corresponding HIV reservoir size, indicating that the reservoirs size is one determinant of the cell capacity to produce virus but that this parameter alone is not sufficient. The patient-dependent heterogeneity in the responses to LRAs could be explained by patient characteristics such as genetic background, time to treatment initiation, duration and type of therapy and also by the gender-specificity, as recently proposed by the team of Jonathan Karn. Sex-based differences in HIV-1 reservoir activity is characterized by a higher cell-associated HIV-1 RNA, higher plasma HIV-1 RNA, higher T-cell activation, and PD-1 expression in men compared to women. The group of Jonathan Karn has shown that the estrogen receptor-1 (ESR-1) is a key regulator of HIV-1 latency. More specifically, antagonists of ESR-1 activate latent HIV-1 proviruses and potentiate HIV-1 reactivation by LRAs such as SAHA, TNFα, and IL-15, while ESR-1 agonists potently block HIV-1 reactivation. Despite a reduced inducible reservoir compared to men, women showed much higher levels of inhibition in response to TCR stimulation in the presence of ESR-1 agonists but exhibited a higher reactivation in response to ESR-1 antagonists when combined with SAHA than the group of male HIV+ individuals. The circadian rhythm is an additional biological process that can affect HIV-1 transcription and reactivation. The circadian rhythm has been first suggested in the clinical trial testing short term administration of disulfiram as a parameter influencing HIV-1 transcription. The authors find an unexpected large variation in pre-dosing CA-US HIV-1 RNA which was statistically significantly higher immediately prior to the first dose of disulfiram than at the two previous time points without changes in HIV-1 DNA or plasma HIV-1 RNA. Indeed, Sharon Lewin and colleagues have subsequently demonstrated a significant time-dependent variation in CA-US HIV-1 RNA in CD4+ T cells from HIV+ individuals on suppressive ART, a variation which is modulated by circadian regulator factors driving transcription from the viral LTR. Thus, in ex vivo studies, the time of blood collection could affect LRA reactivation potency and should be considered to improve latency reversal.

45The multiplicity of mechanisms that regulate HIV-1 latency and the diversity of factors responsible for the heterogeneity of the latent HIV-1 reservoir most likely vary from one patient to the other and even from one cell to the other in a single patient. Indeed, several single-cell studies reported cell-to-cell variability of the latent reservoir and the heterogeneity of cellular response to LRAs. A recent single-cell transcriptome profiling study from Angela Ciuffi laboratory has demonstrated that latently-infected cells are transcriptionally heterogeneous and can be separated into two different cell clusters based on their cellular states. These distinct states correlated with the susceptibility to cellular activation and HIV-1 reactivation, highlighting that the cellular environment could also contribute to the success of HIV-1 reactivation strategies.

Conclusion

46In the frame of the “shock and kill” strategy, clinical trials using LRAs have so far produced unconvincing results. This strategy faces multiple barriers which prevent the complete eradication of replication competent viruses of the HIV-1 reservoir and must, therefore, be optimized. Targeting and reactivating latent cells is challenging due to the heterogeneous nature of the viral reservoirs. Recent studies demonstrating diverse responses of infected cells to LRAs point to their weak effect and highlight the diversity of determinants responsible for the reservoirs’ heterogeneity that were demonstrated so far to be virus genetic background-, cell model-, cell type-, silencing mechanism-, tissue reservoir-, integration site-, patient-, and gender- specific. In addition, some studies demonstrate a heterogeneous effect of LRAs on NK cells and cytotoxic T-cell lymphocyte activity with conflicting observations, suggesting either an immunosuppressive effect or a reduced impact of LRA activity on cells sensing HIV-1 reactivation. Moreover, prolonged ART treatment is associated with a significant reduction in the frequency of HIV-1-specific CD8+ T-cells. Thus, as demonstrated by the group of Robert Siliciano, stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 should be considered for a successful eradication in future clinical trials. Another determinant of the effectiveness of a given LRA in reactivating and purging the viral reservoirs is its ability to efficiently induce latent HIV-1 by targeting not only transcriptional but also post-transcriptional mechanisms that need to be considered for a combined approach of more potent latency reversal. Additionally, an effective LRA needs to penetrate the multitude of HIV-1 tissue reservoirs and sanctuary sites. For instance, it has been shown that panobinostat did not sufficiently penetrate the central nervous system and romidepsin’s concentration in CSF of non-human primate was only 2% of the level found in plasma. Consequently, ensuring a better tissue penetration of LRAs by enhancing the drug delivery system, and most importantly strengthening the killing of the LRA-reactivated cells by stimulating CD8+ T responses are essential for the eradication strategy. Rational design of LRAs considering all these determinants is not possible at the moment, due to the lack of knowledge of all the cellular factors and pathways impacting HIV-1 gene expression and leading to productive viral replication. New approaches including single-cell technologies should be considered to understand why some cells respond to LRAs while others do not as this will be essential for improving the “shock and kill” strategy and hopefully reaching a cure. Moreover, due to the challenges that hinder the effectiveness of the “shock and kill” approach, some attention is also given to strategies aimed at completely suppressing HIV-1 transcription named the “block and lock.” In this context, the Tat inhibitor didehydro-cortistatin A (dCA) has shown its ability to inhibit ex vivo residual viral replication under ART and to prolong the time to viral reactivation after treatment interruption, but some in vitro resistance mutations to dCA were reported. Currently, several drugs are identified for their ability to be used as LPA (Latency Promoting Agents) to ensure a functional cure. Undeniably several strategies must be exploited in order to reach a functional cure. Dealing with the residual viremia and the contribution of ongoing viral replication in the reservoir’s replenishment is one of the major issues. If one of these strategies is promising its efficacy in clinic will be a long process and should, therefore, lead to the formation of a deep latency state preventing viral rebound after ART interruption.

Author Contributions

47AA-A, AK, GD, RV, and CV wrote the manuscript. SD, VG, PM, AM, and OR gave advice and suggestions for the writing of the manuscript.

Conflict of Interest

48The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References 303

1.
Human Galectin-9 Is a Potent Mediator of HIV Transcription and Reactivation. · 2016
Not checked
2.
Abdel-Mohsen M. Kuri-Cervantes L. Grau-Exposito J. Spivak A. M. Nell R. A. Tomescu C. (2018 ). CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells. Sci. Transl. Med. 10:eaar6759.
Not in our library10.1126/scitranslmed.aar6759
3.
Abner E. Stoszko M. Zeng L. Chen H.-C. Izquierdo-Bouldstridge A. Konuma T. (2018 ). A new quinoline BRD4 inhibitor targets a distinct latent HIV-1 reservoir for reactivation from other ‘shock’ drugs. J. Virol. 92:e02056-17.
Not in our library10.1128/jvi.02056-17
4.
Adams M. Sharmeen L. Kimpton J. Romeo J. M. Garcia J. V. Peterlin B. M. (1994 ). Cellular latency in human immunodeficiency virus-infected individuals with high CD4 levels can be detected by the presence of promoter-proximal transcripts. Proc. Natl. Acad. Sci. U.S.A. 91 3862–3866.
Not in our library10.1073/pnas.91.9.3862
5.
Ajamian L. Abel K. Rao S. Vyboh K. García-de-Gracia F. Soto-Rifo R. (2015 ). HIV-1 recruits UPF1 but excludes UPF2 to promote nucleocytoplasmic export of the genomic RNA. Biomolecules 5 2808–2839.
Not in our library10.3390/biom5042808
6.
Almodóvar S. Del C. Colón M. Maldonado I. M. Villafañe R. Abreu S. (2007 ). HIV-1 infection of monocytes is directly related to the success of HAART. Virology 369 35–46.
Not in our library10.1016/j.virol.2007.07.010
7.
Archin N. M. Keedy K. S. Espeseth A. Dang H. Hazuda D. J. Margolis D. M. (2009 ). Expression of latent human immunodeficiency type 1 is induced by novel and selective histone deacetylase inhibitors. AIDS 23 1799–1806.
Not in our library10.1097/qad.0b013e32832ec1dc
8.
Archin N. M. Liberty A. L. Kashuba A. D. Choudhary S. K. Kuruc J. D. Crooks A. M. (2012 ). Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487 482–485.
Not in our library10.1038/nature11286
9.
Avettand-Fenoel V. Hocqueloux L. Müller-Trutwin M. Prazuck T. Melard A. (2011 ). Greater diversity of HIV DNA variants in the rectum compared to variants in the blood in patients without HAART. J. Med. Virol. 83 1499–1507.
Not in our library10.1002/jmv.22132
10.
Banga R. Procopio F. A. Cavassini M. Perreau M. (2016a ). In vitro reactivation of replication-competent and infectious HIV-1 by histone deacetylase inhibitors. J. Virol. 90 1858–1871.
Not in our library10.1128/jvi.02359-15
11.
Banga R. Procopio F. A. Noto A. Pollakis G. Cavassini M. Ohmiti K. (2016b ). PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals. Nat. Med. 22 754–761.
Not in our library10.1038/nm.4113
12.
Blood CXCR3+ CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals · 2018
Not checked
13.
Bartholomeeusen K. Xiang Y. Fujinaga K. Peterlin B. M. (2012 ). Bromodomain and extra-terminal (BET) bromodomain inhibition activate transcription via transient release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein. J. Biol. Chem. 287 36609–36616.
Not in our library10.1074/jbc.m112.410746
14.
Barton K. Hiener B. Winckelmann A. Rasmussen T. A. Shao W. Byth K. (2016 ). Broad activation of latent HIV-1 in vivo. Nat. Commun. 7:12731.
Not in our library10.1038/ncomms12731
15.
Distinct chromatin functional states correlate with HIV latency reactivation in infected primary CD4+ T cells · 2018
No notice
16.
Baxter A. E. Niessl J. Fromentin R. Richard J. Porichis F. Charlebois R. (2016 ). Single-cell characterization of viral translation-competent reservoirs in HIV-infected individuals. Cell Host Microbe 20 368–380.
Not in our library10.1016/j.chom.2016.07.015
17.
Behrens N. E. Wertheimer A. Klotz S. A. Ahmad N. (2018 ). Reduction in terminally differentiated T cells in virologically controlled HIV-infected aging patients on long-term antiretroviral therapy. PLoS One 13:e0199101.
Not in our library10.1371/journal.pone.0199101
18.
Beliakova-Bethell N. Hezareh M. Wong J. K. Strain M. C. Lewinski M. K. Richman D. D. (2017 ). Relative efficacy of T cell stimuli as inducers of productive HIV-1 replication in latently infected CD4 lymphocytes from patients on suppressive cART. Virology 508 127–133.
Not in our library10.1016/j.virol.2017.05.008
19.
Berg S. L. Stone J. Xiao J. J. Chan K. K. Nuchtern J. Dauser R. (2004 ). Plasma and cerebrospinal fluid pharmacokinetics of depsipeptide (FR901228) in nonhuman primates. Cancer Chemother. Pharmacol. 54 85–88.
Not in our library10.1007/s00280-004-0766-5
20.
Blazkova J. Murray D. Justement J. S. Funk E. K. Nelson A. K. Moir S. (2012 ). Paucity of HIV DNA methylation in latently infected, resting CD4+ T cells from infected individuals receiving antiretroviral therapy. J. Virol. 86 5390–5392.
Not in our library10.1128/jvi.00040-12
21.
CpG Methylation Controls Reactivation of HIV from Latency · 2009
No notice
22.
Boehm D. Jeng M. Camus G. Gramatica A. Schwarzer R. Johnson J. R. (2017 ). SMYD2-mediated histone methylation contributes to HIV-1 latency. Cell Host Microbe 21 569–579.e6.
Not in our library10.1016/j.chom.2017.04.011
23.
Bosque A. Nilson K. A. Macedo A. B. Spivak A. M. Archin N. M. Van Wagoner R. M. (2017 ). Benzotriazoles reactivate latent HIV-1 through inactivation of STAT5 SUMOylation. Cell Rep. 18 1324–1334.
Not in our library10.1016/j.celrep.2017.01.022
24.
Bouchat S. Delacourt N. Kula A. Darcis G. Van Driessche B. Corazza F. (2016 ). Sequential treatment with 5-aza-2’-deoxycytidine and deacetylase inhibitors reactivates HIV-1. EMBO Mol. Med. 8 117–138.
Not in our library10.15252/emmm.201505557
25.
Bouchat S. Gatot J.-S. Kabeya K. Cardona C. Colin L. Herbein G. (2012 ). Histone methyltransferase inhibitors induce HIV-1 recovery in resting CD4(+) T cells from HIV-1-infected HAART-treated patients. AIDS 26 1473–1482.
Not in our library10.1097/qad.0b013e32835535f5
26.
Bradley T. Ferrari G. Haynes B. F. Margolis D. M. Browne E. P. (2018 ). Single-cell analysis of quiescent HIV infection reveals host transcriptional profiles that regulate proviral latency. Cell Rep. 25 107–117.e3.
Not in our library10.1016/j.celrep.2018.09.020
27.
Bruner K. M. Murray A. J. Pollack R. A. Soliman M. G. Laskey S. B. Capoferri A. A. (2016 ). Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat. Med. 22 1043–1049.
Not in our library10.1038/nm.4156
28.
Bruner K. M. Wang Z. Simonetti F. R. Bender A. M. Kwon K. J. Sengupta S. (2019 ). A quantitative approach for measuring the reservoir of latent HIV-1 proviruses. Nature 566 120–125.
Not in our library10.1038/s41586-019-0898-8
29.
Budhiraja S. Famiglietti M. Bosque A. Planelles V. Rice A. P. (2013 ). Cyclin T1 and CDK9 T-loop phosphorylation are downregulated during establishment of HIV-1 latency in primary resting memory CD4+ T cells. J. Virol. 87 1211–1220.
Not in our library10.1128/jvi.02413-12
30.
Burnett J. C. Miller-Jensen K. Shah P. S. Arkin A. P. Schaffer D. V. (2009 ). Control of stochastic gene expression by host factors at the HIV promoter. PLoS Pathog. 5:e1000260.
Not in our library10.1371/journal.ppat.1000260
31.
Deep molecular characterization of HIV-1 dynamics under suppressive HAART. · 2011
Not checked
32.
Buzon M. J. Sun H. Li C. Shaw A. Seiss K. Ouyang Z. (2014 ). HIV-1 persistence in CD4+ T cells with stem cell-like properties. Nat. Med. 20 139–142.
Not in our library10.1038/nm.3445
33.
Canaud G. Dejucq-Rainsford N. Avettand-Fenoël V. Viard J.-P. Anglicheau D. Bienaimé F. (2014 ). The kidney as a reservoir for HIV-1 after renal transplantation. J. Am. Soc. Nephrol. 25 407–419.
Not in our library10.1681/asn.2013050564
34.
Canestri A. Lescure F.-X. Jaureguiberry S. Moulignier A. Amiel C. Marcelin A. G. (2010 ). Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin. Infect. Dis. 50 773–778.
Not in our library10.1086/650538
35.
Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa · 2019
No notice
36.
Cao W. Jamieson B. D. Hultin L. E. Hultin P. M. Effros R. B. Detels R. (2009 ). Premature aging of T cells is associated with faster HIV-1 disease progression. J. Acquir. Immune Defic. Syndr. 50 137–147.
Not in our library10.1097/qai.0b013e3181926c28
37.
Caragounis E.-C. Gisslén M. Lindh M. Nordborg C. Westergren S. Hagberg L. (2008 ). Comparison of HIV-1 pol and env sequences of blood, CSF, brain and spleen isolates collected ante-mortem and post-mortem. Acta Neurol. Scand. 117 108–116.
Not in our library10.1111/j.1600-0404.2007.00914.x
38.
Cary D. C. Peterlin B. M. (2018 ). Procyanidin trimer C1 reactivates latent HIV as a triple combination therapy with kansui and JQ1. PLoS One 13:e0208055.
Not in our library10.1371/journal.pone.0208055
39.
Casazza J. P. Betts M. R. Picker L. J. Koup R. A. (2001 ). Decay kinetics of human immunodeficiency virus-specific CD8+ T cells in peripheral blood after initiation of highly active antiretroviral therapy. J. Virol. 75 6508–6516.
Not in our library10.1128/jvi.75.14.6508-6516.2001
40.
Chang C. C. Naranbhai V. Stern J. Roche M. Dantanarayana A. Ke R. (2018 ). Variation in cell-associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator brain-and-muscle-ARNT-like-1. AIDS 32 2119–2128.
Not in our library10.1097/qad.0000000000001937
41.
HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells · 2015
No notice
42.
Chávez L. Kauder S. Verdin E. (2011 ). In vivo, in vitro, and in silico analysis of methylation of the HIV-1 provirus. Methods 53 47–53.
Not in our library10.1016/j.ymeth.2010.05.009
43.
Chen H.-C. Martinez J. P. Zorita E. Meyerhans A. Filion G. J. (2017 ). Position effects influence HIV latency reversal. Nat. Struct. Mol. Biol. 24 47–54.
Not in our library10.1038/nsmb.3328
44.
Chen H.-C. Zorita E. Filion G. J. (2018 ). Using barcoded HIV ensembles (B-HIVE) for single provirus transcriptomics. Curr. Protoc. Mol. Biol. 122:e56.
Not in our library10.1002/cpmb.56
45.
Cherrier T. Le Douce V. Eilebrecht S. Riclet R. Marban C. Dequiedt F. (2013 ). CTIP2 is a negative regulator of P-TEFb. Proc. Natl. Acad. Sci. U.S.A. 110 12655–12660.
Not in our library10.1073/pnas.1220136110
46.
Chomont N. El-Far M. Ancuta P. Trautmann L. Procopio F. A. Yassine-Diab B. (2009 ). HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat. Med. 15 893–900.
Not in our library10.1038/nm.1972
47.
Chun T.-W. Carruth L. Finzi D. Shen X. DiGiuseppe J. A. Taylor H. (1997 ). Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387 183–188.
Not in our library10.1038/387183a0
48.
Chun T.-W. Nickle D. C. Justement J. S. Meyers J. H. Roby G. Hallahan C. W. (2008 ). Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J. Infect. Dis. 197 714–720.
Not in our library10.1086/527324
49.
Cicala C. Martinelli E. McNally J. P. Goode D. J. Gopaul R. Hiatt J. (2009 ). The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proc. Natl. Acad. Sci. U.S.A. 106 20877–20882.
Not in our library10.1073/pnas.0911796106
50.
Clutton G. Xu Y. Baldoni P. L. Mollan K. R. Kirchherr J. Newhard W. (2016 ). The differential short- and long-term effects of HIV-1 latency-reversing agents on T cell function. Sci. Rep. 6:30749.
Not in our library10.1038/srep30749
51.
Clutton G. T. Jones R. B. (2018 ). Diverse impacts of HIV latency-reversing agents on CD8+ T-cell function: implications for HIV cure. Front. Immunol. 9:1452.
Not in our library10.3389/fimmu.2018.01452
52.
Cockerham L. R. Siliciano J. D. Sinclair E. O’Doherty U. Palmer S. Yukl S. A. (2014 ). CD4+ and CD8+ T cell activation are associated with HIV DNA in resting CD4+ T cells. PLoS One 9:e110731.
Not in our library10.1371/journal.pone.0110731
53.
Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies · 2009
No notice
54.
Connick E. Mattila T. Folkvord J. M. Schlichtemeier R. Meditz A. L. Ray M. G. (2007 ). CTL fail to accumulate at sites of HIV-1 replication in lymphoid tissue. J. Immunol. 178 6975–6983.
Not in our library10.4049/jimmunol.178.11.6975
55.
HMBA Releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and Activates HIV Transcription · 2007
No notice
56.
Coombs R. W. Lockhart D. Ross S. O. Deutsch L. Dragavon J. Diem K. (2006 ). Lower genitourinary tract sources of seminal HIV. J. Acquir. Immune Defic. Syndr. 41 430–438.
Not in our library10.1097/01.qai.0000209895.82255.08
57.
Coombs R. W. Reichelderfer P. S. Landay A. L. (2003 ). Recent observations on HIV type-1 infection in the genital tract of men and women. AIDS 17 455–480.
Not in our library10.1097/00002030-200303070-00001
58.
Core L. J. Lis J. T. (2008 ). Transcription regulation through promoter-proximal pausing of RNA polymerase II. Science 319 1791–1792.
Not in our library10.1126/science.1150843
59.
Costiniuk C. T. Jenabian M.-A. (2014 ). The lungs as anatomical reservoirs of HIV infection. Rev. Med. Virol. 24 35–54.
Not in our library10.1002/rmv.1772
60.
Couturier J. Suliburk J. W. Brown J. M. Luke D. J. Agarwal N. Yu X. (2015 ). Human adipose tissue as a reservoir for memory CD4+ T cells and HIV. AIDS 29 667–674.
Not in our library10.1097/qad.0000000000000599
61.
Cribbs S. K. Lennox J. Caliendo A. M. Brown L. A. Guidot D. M. (2015 ). Healthy HIV-1-infected individuals on highly active antiretroviral therapy harbor HIV-1 in their alveolar macrophages. AIDS Res. Hum. Retroviruses 31 64–70.
Not in our library10.1089/aid.2014.0133
62.
Darcis G. Berkhout B. Pasternak A. O. (2019 ). The quest for cellular markers of HIV reservoirs: any color you like. Front. Immunol. 10:2251.
Not in our library10.3389/fimmu.2019.02251
63.
Darcis G. Bouchat S. Kula A. Van Driessche B. Delacourt N. Vanhulle C. (2017 ). Reactivation capacity by latency-reversing agents ex vivo correlates with the size of the HIV-1 reservoir. AIDS 31 181–189.
Not in our library10.1097/qad.0000000000001290
64.
Darcis G. Coombs R. W. Van Lint C. (2016 ). Exploring the anatomical HIV reservoirs: role of the testicular tissue. AIDS 30 2891–2893.
Not in our library10.1097/qad.0000000000001281
65.
An In-Depth Comparison of Latency-Reversing Agent Combinations in Various In Vitro and Ex Vivo HIV-1 Latency Models Identified Bryostatin-1+JQ1 and Ingenol-B+JQ1 to Potently Reactivate Viral Gene Expression · 2015
No notice
66.
Das B. Dobrowolski C. Luttge B. Valadkhan S. Chomont N. Johnston R. (2018 ). Estrogen receptor-1 is a key regulator of HIV-1 latency that imparts gender-specific restrictions on the latent reservoir. Proc. Natl. Acad. Sci. U.S.A. 115 E7795–E7804.
Not in our library10.1073/pnas.1803468115
67.
Davey R. T. Bhat N. Yoder C. Chun T.-W. Metcalf J. A. Dewar R. (1999 ). HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc. Natl. Acad. Sci. U.S.A. 96 15109–15114.
Not in our library10.1073/pnas.96.26.15109
68.
De Scheerder M.-A. Vrancken B. Dellicour S. Schlub T. Lee E. Shao W. (2019 ). HIV rebound is predominantly fueled by genetically identical viral expansions from diverse reservoirs. Cell Host Microbe 26 347–358.e7.
Not in our library10.1016/j.chom.2019.08.003
69.
Debyser Z. Vansant G. Bruggemans A. Janssens J. Christ F. (2018 ). Insight in HIV integration site selection provides a block-and-lock strategy for a functional cure of HIV infection. Viruses 11:E12.
Not in our library10.3390/v11010012
70.
DeChristopher B. A. Loy B. A. Marsden M. D. Schrier A. J. Zack J. A. Wender P. A. (2012 ). Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro. Nat. Chem. 4 705–710.
Not in our library10.1038/nchem.1395
71.
Defining HIV and SIV Reservoirs in Lymphoid Tissues · 2016
No notice
72.
Della Chiara G. Crotti A. Liboi E. Giacca M. Poli G. Lusic M. (2011 ). Negative regulation of HIV-1 transcription by a heterodimeric NF-κB1/p50 and C-terminally truncated STAT5 complex. J. Mol. Biol. 410 933–943.
Not in our library10.1016/j.jmb.2011.03.044
73.
Delwart E. L. Mullins J. I. Gupta P. Learn G. H. Holodniy M. Katzenstein D. (1998 ). Human immunodeficiency virus type 1 populations in blood and semen. J. Virol. 72 617–623.
Not in our library10.1128/jvi.72.1.617-623.1998
74.
Deng K. Pertea M. Rongvaux A. Wang L. Durand C. M. Ghiaur G. (2015 ). Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 517 381–385.
Not in our library10.1038/nature14053
75.
Descours B. Petitjean G. López-Zaragoza J.-L. Bruel T. Raffel R. Psomas C. (2017 ). CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses. Nature 543 564–567.
Not in our library10.1038/nature21710
76.
Desimio M. G. Giuliani E. Doria M. (2017 ). The histone deacetylase inhibitor SAHA simultaneously reactivates HIV-1 from latency and up-regulates NKG2D ligands sensitizing for natural killer cell cytotoxicity. Virology 510 9–21.
Not in our library10.1016/j.virol.2017.06.033
77.
Desimio M. G. Giuliani E. Ferraro A. S. Adorno G. Doria M. (2018 ). In vitro exposure to prostratin but not bryostatin-1 improves natural killer cell functions including killing of CD4+ T cells harboring reactivated human immunodeficiency virus. Front. Immunol. 9:1514.
Not in our library10.3389/fimmu.2018.01514
78.
Diem K. Nickle D. C. Motoshige A. Fox A. Ross S. Mullins J. I. (2008 ). Male genital tract compartmentalization of human immunodeficiency virus type 1 (HIV). AIDS Res. Hum. Retroviruses 24 561–571.
Not in our library10.1089/aid.2007.0115
79.
Ding D. Qu X. Li L. Zhou X. Liu S. Lin S. (2013 ). Involvement of histone methyltransferase GLP in HIV-1 latency through catalysis of H3K9 dimethylation. Virology 440 182–189.
Not in our library10.1016/j.virol.2013.02.022
80.
Doyon G. Zerbato J. Mellors J. W. Sluis-Cremer N. (2013 ). Disulfiram reactivates latent HIV-1 expression through depletion of the phosphatase and tensin homolog. AIDS 27 F7–F11.
Not in our library10.1097/qad.0b013e3283570620
81.
du Chéné I. Basyuk E. Lin Y.-L. Triboulet R. Knezevich A. Chable-Bessia C. (2007 ). Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency. EMBO J. 26 424–435.
Not in our library10.1038/sj.emboj.7601517
82.
Eilebrecht S. Le Douce V. Riclet R. Targat B. Hallay H. Van Driessche B. (2014 ). HMGA1 recruits CTIP2-repressed P-TEFb to the HIV-1 and cellular target promoters. Nucleic Acids Res. 42 4962–4971.
Not in our library10.1093/nar/gku168
83.
Einkauf K. B. Lee G. Q. Gao C. Sharaf R. Sun X. Hua S. (2019 ). Intact HIV-1 proviruses accumulate at distinct chromosomal positions during prolonged antiretroviral therapy. J. Clin. Invest. 129 988–998.
Not in our library10.1172/jci124291
84.
Eisele E. Siliciano R. F. (2012 ). Redefining the viral reservoirs that prevent HIV-1 eradication. Immunity 37 377–388.
Not in our library10.1016/j.immuni.2012.08.010
85.
Elliott J. H. McMahon J. H. Chang C. C. Lee S. A. Hartogensis W. Bumpus N. (2015 ). Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV 2 e520–e529.
Not in our library10.1016/s2352-3018(15)00226-x
86.
Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy · 2014
No notice
87.
Evans V. A. van der Sluis R. M. Solomon A. Dantanarayana A. McNeil C. Garsia R. (2018 ). Programmed cell death-1 contributes to the establishment and maintenance of HIV-1 latency. AIDS 32 1491–1497.
Not in our library10.1097/qad.0000000000001849
88.
Evering T. H. Mehandru S. Racz P. Tenner-Racz K. Poles M. A. Figueroa A. (2012 ). Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection. PLoS Pathog. 8:e1002506.
Not in our library10.1371/journal.ppat.1002506
89.
Fletcher C. V. Staskus K. Wietgrefe S. W. Rothenberger M. Reilly C. Chipman J. G. (2014 ). Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc. Natl. Acad. Sci. U.S.A. 111 2307–2312.
Not in our library10.1073/pnas.1318249111
90.
Forlani G. Tosi G. Turrini F. Poli G. Vicenzi E. Accolla R. S. (2017 ). Tripartite motif-containing protein 22 interacts with class II transactivator and orchestrates its recruitment in nuclear bodies containing TRIM19/PML and cyclin T1. Front. Immunol. 8:564.
Not in our library10.3389/fimmu.2017.00564
91.
Forouzanfar F. Ali S. Wallet C. Rovere M. D. Ducloy C. Mekdad H. E. (2019 ). HIV-1 Vpr mediates the depletion of the cellular repressor CTIP2 to counteract viral gene silencing. Sci. Rep. 9:13154.
Not in our library10.1038/s41598-019-48689-x
92.
Friedman J. Cho W.-K. Chu C. K. Keedy K. S. Archin N. M. Margolis D. M. (2011 ). Epigenetic silencing of HIV-1 by the histone H3 lysine 27 methyltransferase enhancer of zeste 2▽. J. Virol. 85 9078–9089.
Not in our library10.1128/jvi.00836-11
93.
CD4+ T Cells Expressing PD-1, TIGIT and LAG-3 Contribute to HIV Persistence during ART · 2016
No notice
94.
Ganor Y. Real F. Sennepin A. Dutertre C.-A. Prevedel L. Xu L. (2019 ). HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy. Nat. Microbiol. 4 633–644.
Not in our library10.1038/s41564-018-0335-z
95.
Garrido C. Spivak A. M. Soriano-Sarabia N. Checkley M. A. Barker E. Karn J. (2016 ). HIV latency-reversing agents have diverse effects on natural killer cell function. Front. Immunol. 7:356.
Not in our library10.3389/fimmu.2016.00356
96.
Gattinoni L. Lugli E. Ji Y. Pos Z. Paulos C. M. Quigley M. F. (2011 ). A human memory T cell subset with stem cell-like properties. Nat. Med. 17 1290–1297.
Not in our library10.1038/nm.2446
97.
Geng G. Liu B. Chen C. Wu K. Liu J. Zhang Y. (2016 ). Development of an attenuated tat protein as a highly-effective agent to specifically activate HIV-1 latency. Mol. Ther. 24 1528–1537.
Not in our library10.1038/mt.2016.117
98.
Gianella S. Kosakovsky Pond S. L. Oliveira M. F. Scheffler K. Strain M. C. De la Torre A. (2016 ). Compartmentalized HIV rebound in the central nervous system after interruption of antiretroviral therapy. Virus Evol. 2:vew020.
Not in our library10.1093/ve/vew020
99.
Gibellini D. Borderi M. De Crignis E. Cicola R. Cimatti L. Vitone F. (2008 ). HIV-1 DNA load analysis in peripheral blood lymphocytes and monocytes from naïve and HAART-treated individuals. J. Infect. 56 219–225.
Not in our library10.1016/j.jinf.2008.01.001
100.
Gohda J. Suzuki K. Liu K. Xie X. Takeuchi H. Inoue J.-I. (2018 ). BI-2536 and BI-6727, dual Polo-like kinase/bromodomain inhibitors, effectively reactivate latent HIV-1. Sci. Rep. 8:3521.
Not in our library10.1038/s41598-018-21942-5
101.
Golumbeanu M. Cristinelli S. Rato S. Munoz M. Cavassini M. Beerenwinkel N. (2018 ). Single-cell RNA-seq reveals transcriptional heterogeneity in latent and reactivated HIV-infected cells. Cell Rep. 23 942–950.
Not in our library10.1016/j.celrep.2018.03.102
102.
Gosselin A. Monteiro P. Chomont N. Diaz-Griffero F. Said E. A. Fonseca S. (2010 ). Peripheral blood CCR4+CCR6+ and CXCR3+CCR6+CD4+ T cells are highly permissive to HIV-1 infection. J. Immunol. 184 1604–1616.
Not in our library10.4049/jimmunol.0903058
103.
Gosselin A. Wiche Salinas T. R. Planas D. Wacleche V. S. Zhang Y. Fromentin R. (2017 ). HIV persists in CCR6+CD4+ T cells from colon and blood during antiretroviral therapy. AIDS 31 35–48.
Not in our library10.1097/qad.0000000000001309
104.
Gras G. Kaul M. (2010 ). Molecular mechanisms of neuroinvasion by monocytes-macrophages in HIV-1 infection. Retrovirology 7:30.
Not in our library10.1186/1742-4690-7-30
105.
Latency reversal agents affect differently the latent reservoir present in distinct CD4+ T subpopulations · 2019
No notice
106.
Gray C. M. Lawrence J. Schapiro J. M. Altman J. D. Winters M. A. (1999 ). Frequency of class I HLA-restricted anti-HIV CD8+ T cells in individuals receiving highly active antiretroviral therapy (HAART). J. Immunol. 162 1780–1788.
Not in our library
107.
Greger I. H. Demarchi F. Giacca M. Proudfoot N. J. (1998 ). Transcriptional interference perturbs the binding of Sp1 to the HIV-1 promoter. Nucleic Acids Res. 26 1294–1301.
Not in our library10.1093/nar/26.5.1294
108.
Guihot A. Marcelin A.-G. Massiani M.-A. Samri A. Soulié C. Autran B. (2018 ). Drastic decrease of the HIV reservoir in a patient treated with nivolumab for lung cancer. Ann. Oncol. 29 517–518.
Not in our library10.1093/annonc/mdx696
109.
Fimepinostat, a novel dual inhibitor of HDAC and PI3K, effectively reverses HIV-1 latency ex vivo without T cell activation · 2019
Not checked
110.
Hakre S. Chavez L. Shirakawa K. Verdin E. (2012 ). HIV latency: experimental systems and molecular models. FEMS Microbiol. Rev. 36 706–716.
Not in our library10.1111/j.1574-6976.2012.00335.x
111.
Han Y. Lassen K. Monie D. Sedaghat A. R. Shimoji S. Liu X. (2004 ). Resting CD4+ T cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals carry integrated HIV-1 genomes within actively transcribed host genes. J. Virol. 78 6122–6133.
Not in our library10.1128/jvi.78.12.6122-6133.2004
112.
Han Y. Lin Y. B. An W. Xu J. Yang H.-C. O’Connell K. (2008 ). Orientation-dependent regulation of integrated HIV-1 expression by host gene transcriptional readthrough. Cell Host Microbe 4 134–146.
Not in our library10.1016/j.chom.2008.06.008
113.
Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro · 2018
Not checked
114.
Hayashi T. Jean M. Huang H. Simpson S. Santoso N. G. Zhu J. (2017 ). Screening of an FDA-approved compound library identifies levosimendan as a novel anti-HIV-1 agent that inhibits viral transcription. Antiviral Res. 146 76–85.
Not in our library10.1016/j.antiviral.2017.08.013
115.
Heesters B. A. Lindqvist M. Vagefi P. A. Scully E. P. Schildberg F. A. Altfeld M. (2015 ). Follicular dendritic cells retain infectious HIV in cycling endosomes. PLoS Pathog. 11:e1005285.
Not in our library10.1371/journal.ppat.1005285
116.
Hiener B. Horsburgh B. A. Eden J.-S. Barton K. Schlub T. E. Lee E. (2017 ). Identification of genetically intact HIV-1 proviruses in specific CD4+ T cells from effectively treated participants. Cell Rep. 21 813–822.
Not in our library10.1016/j.celrep.2017.09.081
117.
Ho Y.-C. Shan L. Hosmane N. N. Wang J. Laskey S. B. Rosenbloom D. I. S. (2013 ). Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 155 540–551.
Not in our library10.1016/j.cell.2013.09.020
118.
Hogan L. E. Vasquez J. Hobbs K. S. Hanhauser E. Aguilar-Rodriguez B. Hussien R. (2018 ). Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30. PLoS Pathog. 14:e1006856.
Not in our library10.1371/journal.ppat.1006856
119.
Honeycutt J. B. Thayer W. O. Baker C. E. Ribeiro R. M. Lada S. M. Cao Y. (2017 ). HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy. Nat. Med. 23 638–643.
Not in our library10.1038/nm.4319
120.
Houzet L. Pérez-Losada M. Matusali G. Deleage C. Dereuddre-Bosquet N. Satie A.-P. (2018 ). Seminal simian immunodeficiency virus in chronically infected cynomolgus macaques is dominated by virus originating from multiple genital organs. J. Virol. 92:e00133-18.
Not in our library10.1128/jvi.00133-18
121.
Hu Z. Kuritzkes D. R. (2014 ). Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that confer resistance to nonnucleoside reverse transcriptase and integrase strand transfer inhibitors. J. Virol. 88 9268–9276.
Not in our library10.1128/jvi.00695-14
122.
Huang H. Kong W. Jean M. Fiches G. Zhou D. Hayashi T. (2019 ). A CRISPR/Cas9 screen identifies the histone demethylase MINA53 as a novel HIV-1 latency-promoting gene (LPG). Nucleic Acids Res. 47 7333–7347.
Not in our library10.1093/nar/gkz493
123.
Huang H. Liu S. Jean M. Simpson S. Huang H. Merkley M. (2017 ). A novel bromodomain inhibitor reverses HIV-1 latency through specific binding with BRD4 to promote tat and P-TEFb association. Front. Microbiol. 8:1035.
Not in our library10.3389/fmicb.2017.01035
124.
Huang J. Wang F. Argyris E. Chen K. Liang Z. Tian H. (2007 ). Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat. Med. 13 1241–1247.
Not in our library10.1038/nm1639
125.
Immunological biomarkers predict HIV-1 viral rebound after treatment interruption · 2015
No notice
126.
Iglesias-Ussel M. Vandergeeten C. Marchionni L. Chomont N. Romerio F. (2013 ). High levels of CD2 expression identify HIV-1 latently infected resting memory CD4+ T cells in virally suppressed subjects. J. Virol. 87 9148–9158.
Not in our library10.1128/jvi.01297-13
127.
Imai K. Togami H. Okamoto T. (2010 ). Involvement of histone H3 lysine 9 (H3K9) methyltransferase G9a in the maintenance of HIV-1 latency and its reactivation by BIX01294. J. Biol. Chem. 285 16538–16545.
Not in our library10.1074/jbc.m110.103531
128.
Imamichi H. Degray G. Dewar R. L. Mannon P. Yao M. Chairez C. (2011 ). Lack of compartmentalization of HIV-1 quasispecies between the gut and peripheral blood compartments. J. Infect. Dis. 204 309–314.
Not in our library10.1093/infdis/jir259
129.
Iversen A. K. N. Attermann J. Gerstoft J. Fugger L. Mullins J. I. Skinhøj P. (2004 ). Longitudinal and cross-sectional studies of HIV-1 RNA and DNA loads in blood and the female genital tract. Eur. J. Obstet. Gynecol. Reprod. Biol. 117 227–235.
Not in our library10.1016/j.ejogrb.2004.05.016
130.
Jadlowsky J. K. Wong J. Y. Graham A. C. Dobrowolski C. Devor R. L. Adams M. D. (2014 ). Negative elongation factor is required for the maintenance of proviral latency but does not induce promoter-proximal pausing of RNA polymerase II on the HIV long terminal repeat. Mol. Cell Biol. 34 1911–1928.
Not in our library10.1128/mcb.01013-13
131.
Jean M. J. Hayashi T. Huang H. Brennan J. Simpson S. Purmal A. (2017 ). Curaxin CBL0100 blocks HIV-1 replication and reactivation through inhibition of viral transcriptional elongation. Front. Microbiol. 8:2007.
Not in our library10.3389/fmicb.2017.02007
132.
Jenabian M.-A. Costiniuk C. T. Mehraj V. Ghazawi F. M. Fromentin R. Brousseau J. (2016 ). Immune tolerance properties of the testicular tissue as a viral sanctuary site in ART-treated HIV-infected adults. AIDS 30 2777–2786.
Not in our library10.1097/qad.0000000000001282
133.
Jiang G. Espeseth A. Hazuda D. J. Margolis D. M. (2007 ). c-Myc and Sp1 contribute to proviral latency by recruiting histone deacetylase 1 to the human immunodeficiency virus type 1 promoter. J. Virol. 81 10914–10923.
Not in our library10.1128/jvi.01208-07
134.
Jiang G. Mendes E. A. Kaiser P. Sankaran-Walters S. Tang Y. Weber M. G. (2014 ). Reactivation of HIV latency by a newly modified Ingenol derivative via protein kinase Cδ-NF-κB signaling. AIDS 28 1555–1566.
Not in our library10.1097/qad.0000000000000289
135.
Synergistic Reactivation of Latent HIV Expression by Ingenol-3-Angelate, PEP005, Targeted NF-kB Signaling in Combination with JQ1 Induced p-TEFb Activation · 2015
No notice
136.
Jiang G. Nguyen D. Archin N. M. Yukl S. A. Méndez-Lagares G. Tang Y. (2018 ). HIV latency is reversed by ACSS2-driven histone crotonylation. J. Clin. Invest. 128 1190–1198.
Not in our library10.1172/jci98071
137.
A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4+ T-Cells to Recognition by Cytotoxic T-Lymphocytes · 2016
No notice
138.
Histone Deacetylase Inhibitors Impair the Elimination of HIV-Infected Cells by Cytotoxic T-Lymphocytes · 2014
Corrected
139.
Kaiser P. Joshi S. K. Kim P. Li P. Liu H. Rice A. P. (2017 ). Assays for precise quantification of total (including short) and elongated HIV-1 transcripts. J. Virol. Methods 242 1–8.
Not in our library10.1016/j.jviromet.2016.12.017
140.
Kandathil A. J. Sugawara S. Balagopal A. (2016 ). Are T cells the only HIV-1 reservoir? Retrovirology 13:86.
Not in our library10.1186/s12977-016-0323-4
141.
Epigenetic Regulation of HIV-1 Latency by Cytosine Methylation · 2009
No notice
142.
Kessing C. F. Nixon C. C. Li C. Tsai P. Takata H. Mousseau G. (2017 ). In vivo suppression of HIV rebound by didehydro-cortistatin A, a ‘block-and-lock’ strategy for HIV-1 treatment. Cell Rep. 21 600–611.
Not in our library10.1016/j.celrep.2017.09.080
143.
Kim Y. Anderson J. L. Lewin S. R. (2018 ). Getting the “kill” into “shock and kill”: strategies to eliminate latent HIV. Cell Host Microbe 23 14–26.
Not in our library10.1016/j.chom.2017.12.004
144.
HIV-1 TAR element is processed by Dicer to yield a viral micro-RNA involved in chromatin remodeling of the viral LTR · 2007
No notice
145.
Klein K. Nickel G. Nankya I. Kyeyune F. Demers K. Ndashimye E. (2018 ). Higher sequence diversity in the vaginal tract than in blood at early HIV-1 infection. PLoS Pathog. 14:e1006754.
Not in our library10.1371/journal.ppat.1006754
146.
Kohler S. L. Pham M. N. Folkvord J. M. Arends T. Miller S. M. Miles B. (2016 ). Germinal center T follicular helper cells are highly permissive to HIV-1 and alter their phenotype during virus replication. J. Immunol. 196 2711–2722.
Not in our library10.4049/jimmunol.1502174
147.
Kuai Q. Lu X. Qiao Z. Wang R. Wang Y. Ye S. (2018 ). Histone deacetylase inhibitor chidamide promotes reactivation of latent human immunodeficiency virus by introducing histone acetylation. J. Med. Virol. 90 1478–1485.
Not in our library10.1002/jmv.25207
148.
Kula A. Delacourt N. Bouchat S. Darcis G. Avettand-Fenoel V. Verdikt R. (2019 ). Heterogeneous HIV-1 reactivation patterns of disulfiram and combined disulfiram+romidepsin treatments. J. Acquir. Immune Defic. Syndr. 80 605–613.
Not in our library10.1097/qai.0000000000001958
149.
Kula A. Gharu L. Marcello A. (2013 ). HIV-1 pre-mRNA commitment to Rev mediated export through PSF and matrin 3. Virology 435 329–340.
Not in our library10.1016/j.virol.2012.10.032
150.
Kula A. Guerra J. Knezevich A. Kleva D. Myers M. P. Marcello A. (2011 ). Characterization of the HIV-1 RNA associated proteome identifies matrin 3 as a nuclear cofactor of Rev function. Retrovirology 8:60.
Not in our library10.1186/1742-4690-8-60
151.
Kulkosky J. Culnan D. M. Roman J. Dornadula G. Schnell M. Boyd M. R. (2001 ). Prostratin: activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART. Blood 98 3006–3015.
Not in our library10.1182/blood.v98.10.3006
152.
Kulpa D. A. Talla A. Brehm J. H. Ribeiro S. P. Yuan S. Bebin-Blackwell A.-G. (2019 ). Differentiation into an effector memory phenotype potentiates HIV-l latency reversal in CD4+ T cells. J. Virol. 93:e00969-19.
Not in our library10.1128/jvi.00969-19
153.
HIV-1 Latency in Monocytes/Macrophages · 2014
No notice
154.
Laird G. M. Bullen C. K. Rosenbloom D. I. S. Martin A. R. Hill A. L. Durand C. M. (2015 ). Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations. J. Clin. Invest. 125 1901–1912.
Not in our library10.1172/jci80142
155.
Lambotte O. Taoufik Y. de Goër M. G. Wallon C. Goujard C. Delfraissy J. F. (2000 ). Detection of infectious HIV in circulating monocytes from patients on prolonged highly active antiretroviral therapy. J. Acquir. Immune Defic. Syndr. 23 114–119.
Not in our library10.1097/00126334-200002010-00002
156.
Nuclear Retention of Multiply Spliced HIV-1 RNA in Resting CD4+ T Cells · 2006
No notice
157.
Lavolé A. Guihot A. Veyri M. Lambotte O. Autran B. Cloarec N. (2018 ). PD-1 blockade in HIV-infected patients with lung cancer: a new challenge or already a strategy? Ann. Oncol. 29 1065–1066.
Not in our library10.1093/annonc/mdx817
158.
Le Garff G. Samri A. Lambert-Niclot S. Even S. Lavolé A. Cadranel J. (2017 ). Transient HIV-specific T cells increase and inflammation in an HIV-infected patient treated with nivolumab. AIDS 31 1048–1051.
Not in our library10.1097/qad.0000000000001429
159.
Lenasi T. Contreras X. Peterlin B. M. (2008 ). Transcriptional interference antagonizes proviral gene expression to promote HIV latency. Cell Host Microbe 4 123–133.
Not in our library10.1016/j.chom.2008.05.016
160.
Lerner P. Guadalupe M. Donovan R. Hung J. Flamm J. Prindiville T. (2011 ). The gut mucosal viral reservoir in HIV-infected patients is not the major source of rebound plasma viremia following interruption of highly active antiretroviral therapy. J. Virol. 85 4772–4782.
Not in our library10.1128/jvi.02409-10
161.
Leth S. Schleimann M. H. Nissen S. K. Højen J. F. Olesen R. Graversen M. E. (2016 ). Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. Lancet HIV 3 e463–e472.
Not in our library10.1016/s2352-3018(16)30055-8
162.
Lewis M. J. Frohnen P. Ibarrondo F. J. Reed D. Iyer V. Ng H. L. (2013 ). HIV-1 Nef sequence and functional compartmentalization in the gut is not due to differential cytotoxic T lymphocyte selective pressure. PLoS One 8:e75620.
Not in our library10.1371/journal.pone.0075620
163.
Li H. Pauza C. D. (2011 ). HIV envelope-mediated, CCR5/α4β7-dependent killing of CD4-negative γδ T cells which are lost during progression to AIDS. Blood 118 5824–5831.
Not in our library10.1182/blood-2011-05-356535
164.
Long noncoding RNA NRON contributes to HIV-1 latency by specifically inducing tat protein degradation · 2016
No notice
165.
Li Z. Mbonye U. Feng Z. Wang X. Gao X. Karn J. (2018 ). The KAT5-acetyl-histone4-Brd4 axis silences HIV-1 transcription and promotes viral latency. PLoS Pathog. 14:e1007012.
Not in our library10.1371/journal.ppat.1007012
166.
Liang T. Zhang X. Lai F. Lin J. Zhou C. Xu X. (2019 ). A novel bromodomain inhibitor, CPI-203, serves as an HIV-1 latency-reversing agent by activating positive transcription elongation factor b. Biochem. Pharmacol. 164 237–251.
Not in our library10.1016/j.bcp.2019.04.005
167.
López-Huertas M. R. Jiménez-Tormo L. Madrid-Elena N. Gutiérrez C. Rodríguez-Mora S. Coiras M. (2017 ). The CCR5-antagonist maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist bryostatin-1. Sci. Rep. 7:2385.
Not in our library10.1038/s41598-017-02634-y
168.
Lu P. Qu X. Shen Y. Jiang Z. Wang P. Zeng H. (2016 ). The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb. Sci. Rep. 6:24100.
Not in our library10.1038/srep24100
169.
Lu P. Shen Y. Yang H. Wang Y. Jiang Z. Yang X. (2017 ). BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency. Sci. Rep. 7:16646.
Not in our library10.1038/s41598-017-16816-1
170.
Lusic M. Marcello A. Cereseto A. Giacca M. (2003 ). Regulation of HIV-1 gene expression by histone acetylation and factor recruitment at the LTR promoter. EMBO J. 22 6550–6561.
Not in our library10.1093/emboj/cdg631
171.
Madrid-Elena N. García-Bermejo M. L. Serrano-Villar S. Díaz-de Santiago A. Sastre B. Gutiérrez C. (2018 ). Maraviroc is associated with latent HIV-1 reactivation through NF-κB activation in resting CD4+ T cells from HIV-infected individuals on suppressive antiretroviral therapy. J. Virol. 92:e019 31-17.
Not in our library10.1128/jvi.01931-17
172.
Malim M. H. Cullen B. R. (1991 ). HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV-1 latency. Cell 65 241–248.
Not in our library10.1016/0092-8674(91)90158-u
173.
Marban C. Suzanne S. Dequiedt F. de Walque S. Redel L. Van Lint C. (2007 ). Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing. EMBO J. 26 412–423.
Not in our library10.1038/sj.emboj.7601516
174.
Marcelin A.-G. Tubiana R. Lambert-Niclot S. Lefebvre G. Dominguez S. Bonmarchand M. (2008 ). Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma. AIDS 22 1677–1679.
Not in our library10.1097/qad.0b013e32830abdc8
175.
Marini B. Kertesz-Farkas A. Ali H. Lucic B. Lisek K. Manganaro L. (2015 ). Nuclear architecture dictates HIV-1 integration site selection. Nature 521 227–231.
Not in our library10.1038/nature14226
176.
Martin G. E. Pace M. Thornhill J. P. Phetsouphanh C. Meyerowitz J. Gossez M. (2018 ). CD32-expressing CD4 T cells are phenotypically diverse and can contain proviral HIV DNA. Front. Immunol. 9:928.
Not in our library10.3389/fimmu.2018.00928
177.
Massanella M. Bakeman W. Sithinamsuwan P. Fletcher J. L. K. Chomchey N. Tipsuk S. (2019 ). Infrequent HIV infection of circulating monocytes during antiretroviral therapy. J. Virol. 94:e01174-19.
Not in our library10.1128/jvi.01174-19
178.
Mates J. M. de Silva S. Lustberg M. Van Deusen K. Baiocchi R. A. Wu L. (2015 ). A novel histone deacetylase inhibitor, AR-42, reactivates HIV-1 from chronically and latently infected CD4+ T-cells. Retrovirology 7 1–5.
Not in our library10.4137/rrt.s31632
179.
McGary C. S. Deleage C. Harper J. Micci L. Ribeiro S. P. Paganini S. (2017 ). CTLA-4+PD-1- memory CD4+ T cells critically contribute to viral persistence in antiretroviral therapy-suppressed, SIV-infected rhesus macaques. Immunity 47 776–788.e5.
Not in our library10.1016/j.immuni.2017.09.018
180.
McNamara L. A. Onafuwa-Nuga A. Sebastian N. T. Riddell J. Bixby D. Collins K. L. (2013 ). CD133+ hematopoietic progenitor cells harbor HIV genomes in a subset of optimally treated people with long-term viral suppression. J. Infect. Dis. 207 1807–1816.
Not in our library10.1093/infdis/jit118
181.
Miller R. L. Ponte R. Jones B. R. Kinloch N. N. Omondi F. H. Jenabian M.-A. (2019 ). HIV diversity and genetic compartmentalization in blood and testes during suppressive antiretroviral therapy. J. Virol. 93:e00755-19.
Not in our library10.1128/jvi.00755-19
182.
Miyawaki T. Kasahara Y. Taga K. Yachie A. Taniguchi N. (1990 ). Differential expression of CD45RO (UCHL1) and its functional relevance in two subpopulations of circulating TCR-gamma/delta+ lymphocytes. J. Exp. Med. 171 1833–1838.
Not in our library10.1084/jem.171.5.1833
183.
Modai S. Farberov L. Herzig E. Isakov O. Hizi A. Shomron N. (2019 ). HIV-1 infection increases microRNAs that inhibit Dicer1, HRB and HIV-EP2, thereby reducing viral replication. PLoS One 14:e0211111.
Not in our library10.1371/journal.pone.0211111
184.
Mohammadi P. di Iulio J. Muñoz M. Martinez R. Bartha I. Cavassini M. (2014 ). Dynamics of HIV latency and reactivation in a primary CD4+ T cell model. PLoS Pathog. 10:e1004156.
Not in our library10.1371/journal.ppat.1004156
185.
Moron-Lopez S. Kim P. Søgaard O. S. Tolstrup M. Wong J. K. Yukl S. A. (2019 ). Characterization of the HIV-1 transcription profile after romidepsin administration in ART-suppressed individuals. AIDS 33 425–431.
Not in our library10.1097/qad.0000000000002083
186.
Mousseau G. Aneja R. Clementz M. A. Mediouni S. Lima N. S. Haregot A. (2019 ). Resistance to the tat inhibitor didehydro-cortistatin a is mediated by heightened basal HIV-1 transcription. mBio 10:e01750-18.
Not in our library10.1128/mbio.01750-18
187.
Multiple Histone Lysine Methyltransferases Are Required for the Establishment and Maintenance of HIV-1 Latency · 2017
No notice
188.
Nguyen V. T. Kiss T. Michels A. A. Bensaude O. (2001 ). 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414 322–325.
Not in our library10.1038/35104581
189.
Nolan D. J. Rose R. Rodriguez P. H. Salemi M. Singer E. J. Lamers S. L. (2018 ). The spleen is an HIV-1 sanctuary during combined antiretroviral therapy. AIDS Res. Hum. Retroviruses 34 123–125.
Not in our library10.1089/aid.2017.0254
190.
Norton N. J. Mok H. P. Sharif F. Hirst J. C. Lever A. M. L. (2019 ). HIV silencing and inducibility are heterogeneous and are affected by factors intrinsic to the virus. mBio 10:e00188-19.
Not in our library10.1128/mbio.00188-19
191.
Reactivation of latent HIV-1 in central memory CD4+T cells through TLR-1/2 stimulation · 2013
No notice
192.
Offersen R. Nissen S. K. Rasmussen T. A. Østergaard L. Denton P. W. Søgaard O. S. (2016 ). A novel toll-like receptor 9 agonist, MGN1703, enhances HIV-1 transcription and NK cell-mediated inhibition of HIV-1-infected autologous CD4+ T cells. J. Virol. 90 4441–4453.
Not in our library10.1128/jvi.00222-16
193.
Early Antiretroviral Therapy Is Associated with Lower HIV DNA Molecular Diversity and Lower Inflammation in Cerebrospinal Fluid but Does Not Prevent the Establishment of Compartmentalized HIV DNA Populations. · 2017
Not checked
194.
Osuna C. E. Lim S.-Y. Kublin J. L. Apps R. Chen E. Mota T. M. (2018 ). Evidence that CD32a does not mark the HIV-1 latent reservoir. Nature 561 E20–E28.
Not in our library10.1038/s41586-018-0495-2
195.
Directly Infected Resting CD4+T Cells Can Produce HIV Gag without Spreading Infection in a Model of HIV Latency · 2012
No notice
196.
Pache L. Dutra M. S. Spivak A. M. Marlett J. M. Murry J. P. Hwang Y. (2015 ). BIRC2/cIAP1 is a negative regulator of HIV-1 transcription and can be targeted by Smac mimetics to promote reversal of viral latency. Cell Host Microbe 18 345–353.
Not in our library10.1016/j.chom.2015.08.009
197.
Palacios J. A. Pérez-Piñar T. Toro C. Sanz-Minguela B. Moreno V. Valencia E. (2012 ). Long-term nonprogressor and elite controller patients who control viremia have a higher percentage of methylation in their HIV-1 proviral promoters than aviremic patients receiving highly active antiretroviral therapy. J. Virol. 86 13081–13084.
Not in our library10.1128/jvi.01741-12
198.
Pallikkuth S. Sharkey M. Babic D. Z. Gupta S. Stone G. W. Fischl M. A. (2015 ). Peripheral T follicular helper cells are the major HIV reservoir within central memory CD4 T cells in peripheral blood from chronically HIV-infected individuals on combination antiretroviral therapy. J. Virol. 90 2718–2728.
Not in our library10.1128/jvi.02883-15
199.
Paranjpe S. Craigo J. Patterson B. Ding M. Barroso P. Harrison L. (2002 ). Subcompartmentalization of HIV-1 quasispecies between seminal cells and seminal plasma indicates their origin in distinct genital tissues. AIDS Res. Hum. Retroviruses 18 1271–1280.
Not in our library10.1089/088922202320886316
200.
Single-cell characterization and quantification of translation-competent viral reservoirs in treated and untreated HIV infection · 2019
No notice
201.
Passaes C. P. B. Bruel T. Decalf J. David A. Angin M. Monceaux V. (2017 ). Ultrasensitive HIV-1 p24 assay detects single infected cells and differences in reservoir induction by latency reversal agents. J. Virol. 91:e02296-16.
Not in our library10.1128/jvi.02296-16
202.
Penton P. K. Blackard J. T. (2014 ). Analysis of HIV quasispecies suggests compartmentalization in the liver. AIDS Res. Hum. Retroviruses 30 394–402.
Not in our library10.1089/aid.2013.0146
203.
Perreau M. Savoye A.-L. De Crignis E. Corpataux J.-M. Cubas R. Haddad E. K. (2013 ). Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J. Exp. Med. 210 143–156.
Not in our library10.1084/jem.20121932
204.
Piantadosi A. Freije C. A. Gosmann C. Ye S. Park D. Schaffner S. F. (2019 ). Metagenomic sequencing of HIV-1 in the blood and female genital tract reveals little quasispecies diversity during acute infection. J. Virol. 93:e00804-18.
Not in our library10.1128/jvi.00804-18
205.
Pillai S. K. Good B. Pond S. K. Wong J. K. Strain M. C. Richman D. D. (2005 ). Semen-specific genetic characteristics of human immunodeficiency virus type 1 env. J. Virol. 79 1734–1742.
Not in our library10.1128/jvi.79.3.1734-1742.2005
206.
Pomerantz R. J. Trono D. Feinberg M. B. Baltimore D. (1990 ). Cells nonproductively infected with HIV-1 exhibit an aberrant pattern of viral RNA expression: a molecular model for latency. Cell 61 1271–1276.
Not in our library10.1016/0092-8674(90)90691-7
207.
Pulliam L. Gascon R. Stubblebine M. McGuire D. McGrath M. S. (1997 ). Unique monocyte subset in patients with AIDS dementia. Lancet 349 692–695.
Not in our library10.1016/s0140-6736(96)10178-1
208.
Quivy V. Adam E. Collette Y. Demonte D. Chariot A. Vanhulle C. (2002 ). Synergistic activation of human immunodeficiency virus type 1 promoter activity by NF-kappaB and inhibitors of deacetylases: potential perspectives for the development of therapeutic strategies. J. Virol. 76 11091–11103.
Not in our library10.1128/jvi.76.21.11091-11103.2002
209.
Ramakrishnan R. Dow E. C. Rice A. P. (2009 ). Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4(+) T lymphocytes. J. Leukoc. Biol. 86 1345–1350.
Not in our library10.1189/jlb.0509309
210.
Ramakrishnan R. Liu H. Rice A. P. (2015 ). Short communication: SAHA (vorinostat) induces CDK9 Thr-186 (T-loop) phosphorylation in resting CD4+ T cells: implications for reactivation of latent HIV. AIDS Res. Hum. Retroviruses 31 137–141.
Not in our library10.1089/aid.2013.0288
211.
Rao S. Amorim R. Niu M. Temzi A. Mouland A. J. (2018 ). The RNA surveillance proteins UPF1, UPF2 and SMG6 affect HIV-1 reactivation at a post-transcriptional level. Retrovirology 15:42.
Not in our library10.1186/s12977-018-0425-2
212.
Rasmussen T. A. Schmeltz Søgaard O. Brinkmann C. Wightman F. Lewin S. R. Melchjorsen J. (2013 ). Comparison of HDAC inhibitors in clinical development: effect on HIV production in latently infected cells and T-cell activation. Hum. Vaccin. Immunother. 9 993–1001.
Not in our library10.4161/hv.23800
213.
Rasmussen T. A. Tolstrup M. Brinkmann C. R. Olesen R. Erikstrup C. Solomon A. (2014 ). Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV 1 e13–e21.
Not in our library10.1016/s2352-3018(14)70014-1
214.
Rasmussen T. A. Tolstrup M. Møller H. J. Brinkmann C. R. Olesen R. Erikstrup C. (2015 ). Activation of latent human immunodeficiency virus by the histone deacetylase inhibitor panobinostat: a pilot study to assess effects on the central nervous system. Open Forum Infect. Dis. 2:ofv037.
Not in our library10.1093/ofid/ofv037
215.
Synergistic Activation of HIV-1 Expression by Deacetylase Inhibitors and Prostratin: Implications for Treatment of Latent Infection · 2009
No notice
216.
Riou C. Yassine-Diab B. Van grevenynghe J. Somogyi R. Greller L. D. Gagnon D. (2007 ). Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells. J. Exp. Med. 204 79–91.
Not in our library10.1084/jem.20061681
217.
Rochat M. A. Schlaepfer E. Speck R. F. (2017 ). Promising role of toll-like receptor 8 agonist in concert with prostratin for activation of silent HIV. J. Virol. 91:e02084-16.
Not in our library10.1128/jvi.02084-16
218.
Rohr O. Lecestre D. Chasserot-Golaz S. Marban C. Avram D. Aunis D. (2003 ). Recruitment of tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells. J. Virol. 77 5415–5427.
Not in our library10.1128/jvi.77.9.5415-5427.2003
219.
Rothenberger M. K. Keele B. F. Wietgrefe S. W. Fletcher C. V. Beilman G. J. Chipman J. G. (2015 ). Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption. Proc. Natl. Acad. Sci. U.S.A. 112 E1126–E1134.
Not in our library10.1073/pnas.1414926112
220.
Rozera G. Abbate I. Vlassi C. Giombini E. Lionetti R. Selleri M. (2014 ). Quasispecies tropism and compartmentalization in gut and peripheral blood during early and chronic phases of HIV-1 infection: possible correlation with immune activation markers. Clin. Microbiol. Infect. 20 157–166.
Not in our library10.1111/1469-0691.12367
221.
Saayman S. Ackley A. Turner A.-M. W. Famiglietti M. Bosque A. Clemson M. (2014 ). An HIV-encoded antisense long noncoding RNA epigenetically regulates viral transcription. Mol. Ther. 22 1164–1175.
Not in our library10.1038/mt.2014.29
222.
Sadowski I. Hashemi F. B. (2019 ). Strategies to eradicate HIV from infected patients: elimination of latent provirus reservoirs. Cell. Mol. Life Sci. 76 3583–3600.
Not in our library10.1007/s00018-019-03156-8
223.
Salantes D. B. Zheng Y. Mampe F. Srivastava T. Beg S. Lai J. (2018 ). HIV-1 latent reservoir size and diversity are stable following brief treatment interruption. J. Clin. Invest. 128 3102–3115.
Not in our library10.1172/jci120194
224.
Sarracino A. Gharu L. Kula A. Pasternak A. O. Avettand-Fenoel V. Rouzioux C. (2018 ). Posttranscriptional regulation of HIV-1 gene expression during replication and reactivation from latency by nuclear matrix protein MATR3. mBio 9:e02158-18.
Not in our library10.1128/mbio.02158-18
225.
Schlaepfer E. Speck R. F. (2011 ). TLR8 activates HIV from latently infected cells of myeloid-monocytic origin directly via the MAPK pathway and from latently infected CD4+ T cells indirectly via TNF-α. J. Immunol. 186 4314–4324.
Not in our library10.4049/jimmunol.1003174
226.
Schnell G. Price R. W. Swanstrom R. Spudich S. (2010 ). Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection. J. Virol. 84 2395–2407.
Not in our library10.1128/jvi.01863-09
227.
Schröder A. R. W. Shinn P. Chen H. Berry C. Ecker J. R. Bushman F. (2002 ). HIV-1 integration in the human genome favors active genes and local hotspots. Cell 110 521–529.
Not in our library10.1016/s0092-8674(02)00864-4
228.
Microglial Cells: The Main HIV-1 Reservoir in the Brain · 2019
No notice
229.
Scully E. P. Gandhi M. Johnston R. Hoh R. Lockhart A. Dobrowolski C. (2019 ). Sex-based differences in human immunodeficiency virus type 1 reservoir activity and residual immune activation. J. Infect. Dis. 219 1084–1094.
Not in our library10.1093/infdis/jiy617
230.
Scully E. P. Rutishauser R. L. Simoneau C. R. Delagrèverie H. Euler Z. Thanh C. (2018 ). Inconsistent HIV reservoir dynamics and immune responses following anti-PD-1 therapy in cancer patients with HIV infection. Ann. Oncol. 29 2141–2142.
Not in our library10.1093/annonc/mdy259
231.
Sebastian N. T. Zaikos T. D. Terry V. Taschuk F. McNamara L. A. Onafuwa-Nuga A. (2017 ). CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo. PLoS Pathog. 13:e1006509.
Not in our library10.1371/journal.ppat.1006509
232.
Sengupta S. Siliciano R. F. (2018 ). Targeting the latent reservoir for HIV-1. Immunity 48 872–895.
Not in our library10.1016/j.immuni.2018.04.030
233.
Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab · 2019
Not checked
234.
Sewald X. Ladinsky M. S. Uchil P. D. Beloor J. Pi R. Herrmann C. (2015 ). Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection. Science 350 563–567.
Not in our library10.1126/science.aab2749
235.
Shan L. Deng K. Shroff N. S. Durand C. M. Rabi S. A. Yang H.-C. (2012 ). Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 36 491–501.
Not in our library10.1016/j.immuni.2012.01.014
236.
Shen R. Kappes J. C. Smythies L. E. Richter H. E. Novak L. Smith P. D. (2014 ). Vaginal myeloid dendritic cells transmit founder HIV-1. J. Virol. 88 7683–7688.
Not in our library10.1128/jvi.00766-14
237.
Sheth P. M. Kovacs C. Kemal K. S. Jones R. B. Raboud J. M. Pilon R. (2009 ). Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS 23 2050–2054.
Not in our library10.1097/qad.0b013e3283303e04
238.
Siddiqui S. Perez S. Gao Y. Doyle-Meyers L. Foley B. T. Li Q. (2019 ). Persistent viral reservoirs in lymphoid tissues in SIV-infected rhesus macaques of Chinese-origin on suppressive antiretroviral therapy. Viruses 11:E105.
Not in our library10.3390/v11020105
239.
Singh P. K. Plumb M. R. Ferris A. L. Iben J. R. Wu X. (2015 ). LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1 integration to highly spliced genes. Genes Dev. 29 2287–2297.
Not in our library10.1101/gad.267609.115
240.
Sivro A. Schuetz A. Sheward D. Joag V. Yegorov S. Liebenberg L. J. (2018 ). Integrin α4β7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes. Sci. Transl. Med. 10:eaam6354.
Not in our library10.1126/scitranslmed.aam6354
241.
Smith B. A. Gartner S. Liu Y. Perelson A. S. Stilianakis N. I. Keele B. F. (2001 ). Persistence of infectious HIV on follicular dendritic cells. J. Immunol. 166 690–696.
Not in our library10.4049/jimmunol.166.1.690
242.
The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo · 2015
No notice
243.
Sonza S. Mutimer H. P. Oelrichs R. Jardine D. Harvey K. Dunne A. (2001 ). Monocytes harbour replication-competent, non-latent HIV-1 in patients on highly active antiretroviral therapy. AIDS 15 17–22.
Not in our library10.1097/00002030-200101050-00005
244.
Soriano-Sarabia N. Archin N. M. Bateson R. Dahl N. P. Crooks A. M. Kuruc J. D. (2015 ). Peripheral Vγ9Vδ2 T cells are a novel reservoir of latent HIV infection. PLoS Pathog. 11:e1005201.
Not in our library10.1371/journal.ppat.1005201
245.
An In-Depth Comparison of Latent HIV-1 Reactivation in Multiple Cell Model Systems and Resting CD4+ T Cells from Aviremic Patients · 2013
No notice
246.
Spivak A. M. Andrade A. Eisele E. Hoh R. Bacchetti P. Bumpus N. N. (2014 ). A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy. Clin. Infect. Dis. 58 883–890.
Not in our library10.1093/cid/cit813
247.
Spivak A. M. Bosque A. Balch A. H. Smyth D. Martins L. Planelles V. (2015 ). Ex vivo bioactivity and HIV-1 latency reversal by ingenol dibenzoate and panobinostat in resting CD4(+) T cells from aviremic patients. Antimicrob. Agents Chemother. 59 5984–5991.
Not in our library10.1128/aac.01077-15
248.
Spivak A. M. Planelles V. (2018 ). Novel latency reversal agents for HIV-1 cure. Annu. Rev. Med. 69 421–436.
Not in our library10.1146/annurev-med-052716-031710
249.
Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection · 2015
No notice
250.
miR-198 Inhibits HIV-1 Gene Expression and Replication in Monocytes and Its Mechanism of Action Appears To Involve Repression of Cyclin T1 · 2009
No notice
251.
Promoter Targeting shRNA Suppresses HIV-1 Infection In vivo Through Transcriptional Gene Silencing · 2013
Not checked
252.
Tapia G. Højen J. F. Ökvist M. Olesen R. Leth S. Nissen S. K. (2017 ). Sequential Vacc-4x and romidepsin during combination antiretroviral therapy (cART): immune responses to Vacc-4x regions on p24 and changes in HIV reservoirs. J. Infect. 75 555–571.
Not in our library10.1016/j.jinf.2017.09.004
253.
Taura M. Song E. Ho Y.-C. Iwasaki A. (2019 ). Apobec3A maintains HIV-1 latency through recruitment of epigenetic silencing machinery to the long terminal repeat. Proc. Natl. Acad. Sci. U.S.A. 116 2282–2289.
Not in our library10.1073/pnas.1819386116
254.
Tchasovnikarova I. A. Timms R. T. Douse C. H. Roberts R. C. Dougan G. Kingston R. E. (2017 ). Hyperactivation of HUSH complex function by charcot-marie-tooth disease mutation in MORC2. Nat. Genet. 49 1035–1044.
Not in our library10.1038/ng.3878
255.
Tchasovnikarova I. A. Timms R. T. Matheson N. J. Wals K. Antrobus R. Göttgens B. (2015 ). Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells. Science 348 1481–1485.
Not in our library10.1126/science.aaa7227
256.
Telwatte S. Lee S. Somsouk M. Hatano H. Baker C. Kaiser P. (2018 ). Gut and blood differ in constitutive blocks to HIV transcription, suggesting tissue-specific differences in the mechanisms that govern HIV latency. PLoS Pathog. 14:e1007357.
Not in our library10.1371/journal.ppat.1007357
257.
Thorlund K. Horwitz M. S. Fife B. T. Lester R. Cameron D. W. (2017 ). Landscape review of current HIV ‘kick and kill’ cure research - some kicking, not enough killing. BMC Infect. Dis. 17:595.
Not in our library10.1186/s12879-017-2683-3
258.
Thornhill J. P. Pace M. Martin G. E. Hoare J. Peake S. Herrera C. (2019 ). CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype. Mucosal Immunol. 12 1212–1219.
Not in our library10.1038/s41385-019-0180-2
259.
Resting regulatory CD4 T cells: a site of HIV persistence in patients on long-term effective antiretroviral therapy. · 2008
Not checked
260.
Trejbalová K. Kováøová D. Blažková J. Machala L. Jilich D. Weber J. (2016 ). Development of 5′ LTR DNA methylation of latent HIV-1 provirus in cell line models and in long-term-infected individuals. Clin. Epigenetics 8:19.
Not in our library10.1186/s13148-016-0185-6
261.
Triboulet R. Mari B. Lin Y.-L. Chable-Bessia C. Bennasser Y. Lebrigand K. (2007 ). Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science 315 1579–1582.
Not in our library10.1126/science.1136319
262.
Tripathy M. K. McManamy M. E. M. Burch B. D. Archin N. M. Margolis D. M. (2015 ). H3K27 demethylation at the proviral promoter sensitizes latent HIV to the effects of vorinostat in ex vivo cultures of resting CD4+ T cells. J. Virol. 89 8392–8405.
Not in our library10.1128/jvi.00572-15
263.
Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy · 2017
No notice
264.
Turrini F. Marelli S. Kajaste-Rudnitski A. Lusic M. Van Lint C. Das A. T. (2015 ). HIV-1 transcriptional silencing caused by TRIM22 inhibition of Sp1 binding to the viral promoter. Retrovirology 12:104.
Not in our library10.1186/s12977-015-0230-0
265.
Turrini F. Saliu F. Forlani G. Das A. T. Van Lint C. Accolla R. S. (2019 ). Interferon-inducible TRIM22 contributes to maintenance of HIV-1 proviral latency in T cell lines. Virus Res. 269:197631.
Not in our library10.1016/j.virusres.2019.05.009
266.
Tyagi M. Karn J. (2007 ). CBF-1 promotes transcriptional silencing during the establishment of HIV-1 latency. EMBO J. 26 4985–4995.
Not in our library10.1038/sj.emboj.7601928
267.
Valcour V. G. Ananworanich J. Agsalda M. Sailasuta N. Chalermchai T. Schuetz A. (2013 ). HIV DNA reservoir increases risk for cognitive disorders in cART-naïve patients. PLoS One 8:e70164.
Not in our library10.1371/journal.pone.0070164
268.
Valcour V. G. Shiramizu B. T. Shikuma C. M. (2010 ). HIV DNA in circulating monocytes as a mechanism to dementia and other HIV complications. J. Leukoc. Biol. 87 621–626.
Not in our library10.1189/jlb.0809571
269.
Valcour V. G. Shiramizu B. T. Sithinamsuwan P. Nidhinandana S. Ratto-Kim S. Ananworanich J. (2009 ). Asia research collaboration with the University of Hawaii 001 protocol team. HIV DNA and cognition in a thai longitudinal HAART initiation cohort: the SEARCH 001 cohort study. Neurology 72 992–998.
Not in our library10.1212/01.wnl.0000344404.12759.83
270.
van der Hoek L. Sol C. J. Maas J. Lukashov V. V. Kuiken C. L. Goudsmit J. (1998 ). Genetic differences between human immunodeficiency virus type 1 subpopulations in faeces and serum. J. Gen. Virol. 79(Pt 2), 259–267.
Not in our library10.1099/0022-1317-79-2-259
271.
HIV-1 transcription and latency: an update · 2013
No notice
272.
Van Lint C. Emiliani S. Ott M. Verdin E. (1996 ). Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation. EMBO J. 15 1112–1120.
Not in our library10.1002/j.1460-2075.1996.tb00449.x
273.
Venanzi Rullo E. Cannon L. Pinzone M. R. Ceccarelli M. Nunnari G. O’Doherty U. (2019 ). Genetic evidence that Naïve T cells can contribute significantly to the HIV intact reservoir: time to re-evaluate their role. Clin. Infect. Dis. 69 2236–2237.
Not in our library10.1093/cid/ciz378
274.
Verdin E. Paras P. Van Lint C. (1993 ). Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation. EMBO J. 12 3249–3259.
Not in our library10.1002/j.1460-2075.1993.tb05994.x
275.
Vibholm L. K. Lorenzi J. C. C. Pai J. A. Cohen Y. Z. Oliveira T. Y. Barton J. P. (2019 ). Characterization of intact proviruses in blood and lymph node from HIV-infected individuals undergoing analytical treatment interruption. J. Virol. 93:e01920-18.
Not in our library10.1128/jvi.01920-18
276.
von Stockenstrom S. Odevall L. Lee E. Sinclair E. Bacchetti P. Killian M. (2015 ). Longitudinal genetic characterization reveals that cell proliferation maintains a persistent HIV type 1 DNA pool during effective HIV therapy. J. Infect. Dis. 212 596–607.
Not in our library10.1093/infdis/jiv092
277.
Vranckx L. S. Demeulemeester J. Saleh S. Boll A. Vansant G. Schrijvers R. (2016 ). LEDGIN-mediated inhibition of integrase-LEDGF/p75 interaction reduces reactivation of residual latent HIV. EBioMedicine 8 248–264.
Not in our library10.1016/j.ebiom.2016.04.039
278.
Walker-Sperling V. E. Pohlmeyer C. W. Tarwater P. M. Blankson J. N. (2016 ). The effect of latency reversal agents on primary CD8+ T cells: implications for shock and kill strategies for human immunodeficiency virus eradication. EBioMedicine 8 217–229.
Not in our library10.1016/j.ebiom.2016.04.019
279.
Wan Z. Chen X. (2014 ). Triptolide inhibits human immunodeficiency virus type 1 replication by promoting proteasomal degradation of Tat protein. Retrovirology 11:88.
Not in our library10.1186/s12977-014-0088-6
280.
Weber S. Weiser B. Kemal K. S. Burger H. Ramirez C. M. Korn K. (2014 ). Epigenetic analysis of HIV-1 proviral genomes from infected individuals: predominance of unmethylated CpG’s. Virology 449 181–189.
Not in our library10.1016/j.virol.2013.11.013
281.
Wei P. Garber M. E. Fang S. M. Fischer W. H. Jones K. A. (1998 ). A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA. Cell 92 451–462.
Not in our library10.1016/s0092-8674(00)80939-3
282.
Weinberger L. S. Burnett J. C. Toettcher J. E. Arkin A. P. Schaffer D. V. (2005 ). Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Cell 122 169–182.
Not in our library10.1016/j.cell.2005.06.006
283.
Weng K.-F. Hung C.-T. Hsieh P.-T. Li M.-L. Chen G.-W. Kung Y. A. (2014 ). A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells. Nucleic Acids Res. 42 12789–12805.
Not in our library10.1093/nar/gku952
284.
Wightman F. Lu H. K. Solomon A. E. Saleh S. Harman A. N. Cunningham A. L. (2013 ). Entinostat is a histone deacetylase inhibitor selective for class 1 histone deacetylases and activates HIV production from latently infected primary T cells. AIDS 27 2853–2862.
Not in our library10.1097/qad.0000000000000067
285.
Wightman F. Solomon A. Khoury G. Green J. A. Gray L. Gorry P. R. (2010 ). Both CD31(+) and CD31- naive CD4(+) T cells are persistent HIV type 1-infected reservoirs in individuals receiving antiretroviral therapy. J. Infect. Dis. 202 1738–1748.
Not in our library10.1086/656721
286.
Wightman F. Solomon A. Kumar S. S. Urriola N. Gallagher K. Hiener B. (2015 ). Effect of ipilimumab on the HIV reservoir in an HIV-infected individual with metastatic melanoma. AIDS 29 504–506.
Not in our library10.1097/qad.0000000000000562
287.
Williams D. W. Veenstra M. Gaskill P. J. Morgello S. Calderon T. M. Berman J. W. (2014 ). Monocytes mediate HIV neuropathogenesis: mechanisms that contribute to HIV associated neurocognitive disorders. Curr. HIV Res. 12 85–96.
Not in our library10.2174/1570162x12666140526114526
288.
Williams S. A. Chen L.-F. Kwon H. Ruiz-Jarabo C. M. Verdin E. Greene W. C. (2006 ). NF-kappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J. 25 139–149.
Not in our library10.1038/sj.emboj.7600900
289.
Winckelmann A. Barton K. Hiener B. Schlub T. E. Shao W. Rasmussen T. A. (2017 ). Romidepsin-induced HIV-1 viremia during effective antiretroviral therapy contains identical viral sequences with few deleterious mutations. AIDS 31 771–779.
Not in our library10.1097/qad.0000000000001400
290.
Winckelmann A. Morcilla V. Shao W. Schleimann M. H. Hojen J. F. Schlub T. E. (2018 ). Genetic characterization of the HIV-1 reservoir after Vacc-4x and romidepsin therapy in HIV-1-infected individuals. AIDS 32 1793–1802.
Not in our library10.1097/qad.0000000000001861
291.
Winston J. A. Bruggeman L. A. Ross M. D. Jacobson J. Ross L. D’Agati V. D. (2001 ). Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N. Engl. J. Med. 344 1979–1984.
Not in our library10.1056/nejm200106283442604
292.
Xing S. Bullen C. K. Shroff N. S. Shan L. Yang H.-C. Manucci J. L. (2011 ). Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation. J. Virol. 85 6060–6064.
Not in our library10.1128/jvi.02033-10
293.
Yamaguchi Y. Takagi T. Wada T. Yano K. Furuya A. Sugimoto S. (1999 ). NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell 97 41–51.
Not in our library10.1016/s0092-8674(00)80713-8
294.
Yang W. Sun Z. Hua C. Wang Q. Xu W. Deng Q. (2018 ). Chidamide, a histone deacetylase inhibitor-based anticancer drug, effectively reactivates latent HIV-1 provirus. Microbes Infect. 20 626–634.
Not in our library10.1016/j.micinf.2017.10.003
295.
Yang Z. Zhu Q. Luo K. Zhou Q. (2001 ). The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414 317–322.
Not in our library10.1038/35104575
296.
Ylisastigui L. Archin N. M. Lehrman G. Bosch R. J. Margolis D. M. (2004 ). Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression. AIDS 18 1101–1108.
Not in our library10.1097/00002030-200405210-00003
297.
Yucha R. W. Hobbs K. S. Hanhauser E. Hogan L. E. Nieves W. Ozen M. O. (2017 ). High-throughput characterization of HIV-1 reservoir reactivation using a single-cell-in-droplet PCR assay. EBioMedicine 20 217–229.
Not in our library10.1016/j.ebiom.2017.05.006
298.
Yukl S. A. Kaiser P. Kim P. Telwatte S. Joshi S. K. Vu M. (2018 ). HIV latency in isolated patient CD4+ T cells may be due to blocks in HIV transcriptional elongation, completion, and splicing. Sci. Transl. Med. 10:eaa9927.
Not in our library10.1126/scitranslmed.aap9927
299.
Yukl S. A. Shergill A. K. Ho T. Killian M. Girling V. Epling L. (2013 ). The distribution of HIV DNA and RNA in cell subsets differs in gut and blood of HIV-positive patients on ART: implications for viral persistence. J. Infect. Dis. 208 1212–1220.
Not in our library10.1093/infdis/jit308
300.
Hematopoietic Stem and Progenitor Cells Are a Distinct HIV Reservoir that Contributes to Persistent Viremia in Suppressed Patients · 2018
Not checked
301.
Zapata J. C. Campilongo F. Barclay R. A. DeMarino C. Iglesias-Ussel M. D. Kashanchi F. (2017 ). The human immunodeficiency virus 1 ASP RNA promotes viral latency by recruiting the polycomb repressor complex 2 and promoting nucleosome assembly. Virology 506 34–44.
Not in our library10.1016/j.virol.2017.03.002
302.
Zerbato J. M. McMahon D. K. Sobolewski M. D. Mellors J. W. Sluis-Cremer N. (2019 ). Naïve CD4+ T cells harbor a large inducible reservoir of latent, replication-competent HIV-1. Clin. Infect. Dis. 69 1919–1925.
Not in our library10.1093/cid/ciz108
303.
Zhang Z. Nikolai B. C. Gates L. A. Jung S. Y. Siwak E. B. He B. (2017 ). Crosstalk between histone modifications indicates that inhibition of arginine methyltransferase CARM1 activity reverses HIV latency. Nucleic Acids Res. 45 9348–9360.
Not in our library10.1093/nar/gkx550

Cited by papers we hold 2

Extracellular Vesicles as a New Promising Therapy in HIV Infection · 2022
Not checked
Flower power: Locking HIV in the gut with French lilac · 2021
Not checked

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.