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Evasion of Influenza A Viruses from Innate and Adaptive Immune Responses

Carolien E. Van de Sandt, Joost H. C. M. Kreijtz, Guus F. Rimmelzwaan

Viruses · 2012 · Review

Abstract

The influenza A virus is one of the leading causes of respiratory tract infections in humans. Upon infection with an influenza A virus, both innate and adaptive immune responses are induced. Here we discuss various strategies used by influenza A viruses to evade innate immune responses and recognition by components of the humoral and cellular immune response, which consequently may result in reduced clearing of the virus and virus-infected cells. Finally, we discuss how the current knowledge about immune evasion can be used to improve influenza A vaccination strategies.

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From PubMed Central, U.S. National Library of Medicine, as current on Oct 20, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

1Influenza viruses belong to the family of orthomyxoviridae and are one of the leading causes of respiratory tract infections in humans. Yearly, influenza viruses cause an estimated 3–5 million severe clinical infections and 250,000–500,000 fatal cases. The genome of influenza A viruses consists of eight gene segments of single-stranded negative-sense RNA encoding 12 proteins: surface glycoproteins, hemaglutinin (HA) and neuraminidase (NA), two matrix proteins (M1 and M2), the nucleoprotein (NP), three polymerase complex proteins PB1, PB2 and PA, and four non-structural proteins NS1, NS2, PA-X and PB1-F2.

2Influenza A viruses are subdivided, based on their surface glycoproteins; currently 17 subtypes of HA and nine subtypes of NA are known. Seasonal influenza A viruses of the H1N1 and H3N2 subtype and influenza B viruses cause yearly epidemics. This can be attributed to their ability to escape recognition by virus specific antibodies due to antigenic drift (Figure 1). As a result, seasonal influenza vaccines need to be updated almost annually to match the new epidemic strains and to remain efficacious.

3Introduction in the human population of influenza A viruses with antigenically distinct HA molecules, including novel subtypes, is known as antigenic shift (Figure 1). When such an antigenically-distinct virus is transmitted efficiently from human to human, it may cause a pandemic influenza outbreak, since neutralizing antibodies to this virus are absent in the population at large. Examples of pandemics include the Spanish flu of 1918 caused by a virus of the H1N1 subtype which killed 20–50 million people, the Asian flu of 1957 caused by a re-assorted H2N2 virus and the Hong Kong flu of 1968 caused by a re-assorted H3N2 virus. Each time, the pandemic virus replaced the subtype that circulated prior to the pandemic. In 1977, a virus of the H1N1 subtype was re-introduced, which did not result in a major pandemic, and this virus seasonally co-circulated with the H3N2 virus subtype until 2009. The first pandemic outbreak of the 21st century occurred in 2009 when a novel H1N1 re-assorted virus of swine origin was introduced into the human population. In addition, other influenza virus subtypes are transmitted from animals (in particular swine and avian influenza viruses) to humans occasionally. For example, in 1999, there were three isolated cases of influenza A/H9N2 virus infections in humans displaying mild symptoms only. During an outbreak of highly pathogenic avian influenza A virus of the H7N7 subtype in the Netherlands in 2003, 89 human cases were reported of which one was fatal. Larger is the impact of highly pathogenic avian influenza A/H5N1 viruses which have been transmitted on a regular basis from infected poultry to man since the first case was identified in 1997 in Hong Kong. Since 2003, over 600 human cases have been reported, most of them suffering from severe pneumonia progressing to acute respiratory distress syndrome, 60% of the cases had a fatal outcome. The reported case fatality rate most likely is an overestimate, since subclinical infections and mild cases are not reported. So far, efficient human-to-human transmission has not been observed, although clusters of human cases have been reported. Furthermore, recent studies have shown that, in principle, transmission of highly pathogenic H5N1 viruses amongst mammals is possible and that only a limited number of adaptive mutations are required for airborne transmission, emphasizing the pandemic potential of these viruses.

4Without lifelong protection against seasonal influenza virus infections and the threat of possible future pandemics, it is of great importance to have insight in how immunity against influenza A infections is formed and how influenza A viruses manage to evade these immune responses. In this review, we describe the role of innate and adaptive immunity against influenza A virus infections and evasion strategies used by influenza A viruses to escape immunity. Finally, we briefly discuss the impact on influenza A vaccine development.

2. Innate Immunity

5The primary targets for influenza viruses are the epithelial cells that line the respiratory tract and which initiate an antiviral immune response upon detection of the virus. The first line of defense is formed by the innate immune system, which is quick but lacks specificity and memory. Innate immunity is formed by physical barriers (e.g., mucus and collectins) and innate cellular immune responses. Here, we outline several of the innate defense mechanisms directed against influenza A infections.

2.1. Sensing Of Influenza Virus Infection by Receptors of the Innate Immune System

6Influenza A virus infection results in the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) that initiate antiviral signaling cascades, resulting in the production of interferons (IFNs), cytokines and chemokines. Three main categories of PRRs are involved in recognition of an influenza A infection and the induction of an IFN response: Toll like receptors (TLRs), retinoic acid inducible gene-I (RIG-I) receptors and nucleotide oligomerization domain(NOD)-like receptor family pyrin domain containing 3 (NLRP3).

7The TLRs are the first receptors to recognize the influenza virus infection. TLR7 is an intracellular receptor that recognizes single stranded viral RNA (ssRNA) after the ribonucleoprotein complex has been degraded inside acidified endosomes. TLR3 is another intracellular receptor that recognizes double stranded viral RNA (dsRNA). Other TLR receptors likely to sense an influenza virus infection are TLR2 and TLR4, which are present on the cell surface and recognize viral surface glycoproteins like influenza HA and NA. At a later stage of infection, newly produced uncapped, 5'-triphosphates bearing viral RNAs are recognized by RIG-I receptors in the cytoplasm.

8NLRP3 is part of the NLRP3 inflammasome and is activated by dsRNA which subsequently activates caspase I, resulting in the proteolytic maturation of IL-1β and IL-18.

9The signaling cascade of all activated TLRs, except for TLR3, starts with the activation of MyD88, which subsequently can activate tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), either directly or via IL-1R-associated kinase-1 (IRAK 1), eventually leading to the activation of mitogen-activated kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). TLR3 signaling cascade starts with the activation of TRIF (TIR-domain-containing adapter‑inducing interferon-β) eventually activating NF-κB and interferon regulatory factor 3 (IRF3). TLR4 can also signal via the TRIF dependent pathway by formation of a TRAM-TRIF complex.

10Activation of RIG-I receptor by binding of viral 5'-triphosphates RNA or viral dsRNA to the repressor domain (RD) of RIG-I results in conformational changes exposing the caspase activation and recruitment domains (CARDs). These domains are ubiquitinated by IFN-inducible E3 ubiquitin ligase, tripartite motif 25 (TRIM25). RIG-I can then associate with mitochondrial antiviral signaling adaptor (MAVS; also known as IPS-1, VISA or Cardif), starting a signaling cascade that leads to the activation of IRF3 and NF-κB. The signaling cascades via TLRs and RIG-I receptors have been extensively reviewed by others (Figure 2).

11All these pathways eventually result in the transcription of proinflammatory cytokines, chemokines and IFNs that activate the antiviral response and the recruitment of neutrophils, activation of macrophages and maturation of dendritic cells (DCs). So far, three IFN types have been identified. Type I IFNs include IFN-α and IFN-β which have an important role in limiting viral replication. Type I interferons secreted by infected cells act on IFN-α/β receptors (IFN-α/βR) of the same cell or neighboring cells, activating an antiviral signaling cascade that involves phosphorylation of tyrosine kinase 2 (Tyk2) and Janus kinase 1 (Jak1), also called, “just another kinase 1”, which then phosphorylate signal transducer and activators of transcription (STAT) 1 and STAT2. Phosphorylated STAT1 and 2 combine with IRF9 to form ISGF3 (IFN-stimulated gene factor-3 transcription factor complex) which is responsible for the transcription of >300 genes that encode for e.g., antiviral proteins (Table 1) that establish an antiviral state in the cell that limits viral replication (Figure 3). IFN-β acts through a positive feedback loop on the IFN-β receptor which activates IFN stimulated gene factor 3 (ISGF3), resulting in the expression of IRF-7. IRF-7 is phosphorylated in the presence of a viral infection and induces the expression of both IFN-α and IFN-β.

12IFN-γ is the main type II IFN and contributes to the establishment of an effective adaptive cytotoxic T cell (CTL) response against the influenza virus infection. It regulates virus-specific CTL homeostasis in secondary lymph nodes and subsequent trafficking of CTLs to the site of infection. Furthermore, IFN-γ plays an important role in memory CTL responses. Type III IFNs, like IFN-λ, also control influenza A infections in the lung.

2.2. Macrophages

13During homeostasis, alveolar macrophages exhibit a relatively quiescent state, producing only low levels of cytokines, and suppress the induction of innate and adaptive immunity. CCL2, produced by infected epithelial cells during the initial phase of the influenza virus infection, attracts alveolar macrophages and monocytes via their CCR2 receptor. Activated macrophages enhance their pro-inflammatory cytokine response, including IL-6 and TNF-α. Alveolar macrophages have a direct role in limiting viral spread by phagocytosis of apoptotic infected cells and by phagocyte-mediated opsonophagocytosis of influenza virus particles. They are also involved in regulating the adaptive immune response. Depletion of alveolar macrophages prior to influenza virus infection led to a reduction of antibody titers and reduced numbers of virus-specific CTLs post-infection. In contrast to these beneficial effects, alveolar macrophages also pose a negative effect, since their activation also results in the production of nitric oxide synthase 2 (NOS2) and TNF-α which contribute to the severe pathology that can be the result of an influenza virus infection.

2.3. Natural Killer Cells

14Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system. They are able to lyse infected cells in a MHC class I independent manner via a direct or indirect mechanism of recognition. The sialylated NKp44 and NKp46 receptors are bound by the HA proteins expressed on the surface of influenza virus-infected cells. This results in direct lysis of the infected cell. It was shown that mice lacking the NKp46 receptor equivalent, NCR-1, displayed increased morbidity and mortality following influenza A infection. NK cells with their CD16 receptor (FcγRIII) can bind to the Fc portion of antibodies bound to influenza virus-infected cells and mediate lysis of these cells. This process is known as antibody-dependent cell cytotoxicity (ADCC).

2.4. Dendritic Cells

15Dendritic cells (DCs) are professional antigen presenting cells (APCs) which form an important bridge between the innate and the adaptive immune system. During an infection, DCs initiate adaptive immune responses by the presentation of viral antigens to naïve and memory T and B lymphocytes (Figure 4). At steady state conditions, DCs constantly survey the lungs for invading pathogens or foreign material. Once the lungs are infected with influenza A virus, the DCs can acquire the antigens via two distinct mechanisms. The first route is by direct infection of DCs by influenza A virus. Proteasomes in the cytosol degrade viral proteins into small peptides which are transported to the endoplasmic reticulum (ER) via TAP (transporter of antigen processing), where they are loaded to MHC class I molecules. These MHC class I peptide complexes are then transported via the Golgi complex onto the cell membrane where they can be recognized by virus-specific CD8+ cytotoxic T cells (CTLs) (Figure 5). The second mechanism of antigen acquisition by DCs is through phagocytosis of virus particles or apoptotic epithelial cells. Viral proteins are then degraded into smaller peptides in endosomes/lysosomes and presented on the cell surface in MHC class II peptide complexes which can be recognized by CD4+ T helper cells. T helper cells assist B cells to proliferate and mature into antibody-producing plasma cells. Via this route of antigen acquisition, DCs can also present epitopes to CD8+ T cells. This is also known as cross-presentation. For presentation of viral antigens to virus-specific T cells, activated DCs migrate to the draining lymph nodes.

3. Adaptive Immunity

16The second line of defense against influenza A virus infection is the adaptive immune response. Overall, this highly specific response is relatively slow upon first encounter with a pathogen. However, as a result of the formation of immunological memory, the response is faster and stronger after a second encounter with the same pathogen. The adaptive immune response consists of humoral (virus‑specific antibodies) and cellular (virus-specific CD4+ and CD8+ T cells) immunity. Here we summarize virus-specific recognition by components of the adaptive immune system and their contribution to clearance of influenza A virus infections.

3.1. Humoral Immunity

17Influenza virus infection induces the production of influenza virus-specific antibodies by B cells. In particular, antibodies directed to the viral HA and NA correlate with protective immunity.

18Antibodies directed to the trimeric globular head of HA can afford sterilizing immunity to influenza virus infection. By binding to the HA receptor binding site located in this region they can block virus attachment to host cells and/or block receptor-mediated endocytosis. However, most antibodies directed against HA are influenza virus strain-specific and fail to neutralize intrasubtypic drift variants and viruses of other subtypes. This is mainly due to the high variability in the HA globular head (see below). Of interest, humoral immunity elicited after an influenza virus infection does provide long-lasting antibody mediated protection against the strains that resemble the infected strain. This was exemplified during the pandemic of 2009 caused by an influenza virus of the H1N1 subtype. Elderly people that were exposed to influenza A/H1N1 virus in the 1950s had antibodies which cross-reacted with the pandemic strain and were relatively spared from contracting infections and developing disease. Recently, broadly reacting antibodies directed against the conserved stem region of HA have been identified.

19Antibodies to the other major glycoprotein, the viral NA, interfere with the last phase of the viral replication cycle and also exert protective immunity. NA is a sialydase and removes sialic acids from infected cells and budded virions, thereby facilitating efficient release and spread of newly formed viral particles. Unlike HA-specific antibodies, NA-specific antibodies do not neutralize the virus. However, by inhibiting the enzymatic activity of NA, these antibodies limit the viral spread and thus shorten severity and duration of illness. Furthermore, NA-specific antibodies may also contribute to clearance of virus-infected cells by facilitating ADCC.

20In addition to HA and NA, influenza virus particles contain the minor glycoprotein M2. This tetrameric transmembrane protein has ion channel activity and plays an important role in unpacking the virus in the endosome. A protective effect of M2-specific antibodies was first demonstrated in mice after passive transfer of M2-specific monoclonal antibodies. M2-specific antibodies facilitate ADCC. Since the M2 protein is highly conserved between various influenza A virus subtypes, M2-specific antibodies are likely to afford heterosubtypic immunity.

21After infection, antibodies are also induced against other viral proteins, including NP. Since NP is highly conserved between influenza A viruses, these antibodies could potentially contribute to heterosubtypic immunity. Although NP-specific antibodies are non-neutralizing, it was shown in mice that they contribute to protective immunity. However, their mode of action is poorly understood, but may include ADCC of infected cells and opsonisation of NP, resulting in improved T cell responses.

22After primary infection with influenza virus, serum antibodies of the IgM, IgA and IgG isotypes are induced, whereas after secondary responses, IgM responses are not observed. IgM antibodies can neutralize the virus, but also activate the complement system. In humans, virus-specific serum IgA responses seem indicative for recent infection with influenza virus. Virus‑specific IgG antibodies correlate with long-lived protection, provided that the antibodies match the strains causing the infection. In addition to serum antibodies, influenza virus infection also induces local mucosal sIgA antibody responses that protect airway epithelial cells from infection.

23Young infants may be protected from influenza virus infection by maternal antibodies, when they match the incoming virus.

3.2. Cellular Immunity

24Influenza A virus infection induces a cellular immune response, including virus-specific CD4+ T cells and CD8+ T cells. These cells play an important role in regulation of the immune response and viral clearance respectively.

3.2.1. CD4+ T Cells

25CD4+ T cells are activated after recognition of viral epitopes associated with MHC class II molecules and interaction with co-stimulatory molecules on APCs. Depending on the cytokine milieu, activation of naïve CD4+ T cells can result in the differentiation into CD4+ T helper 1 cells (Th1) or Th2, which can be distinguished based on their cytokine expression profiles. Th2 cells produce IL-4, IL-5 and IL-13 and promote the activation and differentiation of B cells, resulting in antibody production. The antibody response is strengthened by the induction of antibody class switching and somatic hypermutations affecting the variable region of the antibody, resulting in affinity maturation of the influenza-specific antibodies. Th1 cells produce IFN-γ and IL-2 and are mainly involved in promoting CTL responses, and are essential for the induction of memory CD8+ T cells. Memory CD4+ T cells, induced after a primary influenza A virus infection, contribute to faster control of subsequent influenza A virus infections. Lung-resident memory CD4+ T cells in particular have an important role in protection against secondary influenza A virus infections. In addition to helper function, CD4+ T cells also display cytolytic activity. It was shown that these cells play a role in protective immunity against influenza A virus infections in humans. A more extensive review on the role of CD4+ T cells in heterosubtypic immunity can be found elsewhere.

3.2.2. CD8+ T Cells

26Naïve CD8+ T cells are activated after recognition of viral epitopes associated with MHC class I molecules on APCs in the draining lymph nodes, and subsequently differentiate into CTLs. These CTLs migrate to the site of infection where they recognize and eliminate influenza virus infected cells and thereby prevent the production and spread of progeny virus. Human influenza virus-specific CTLs are mainly directed against epitopes of the highly conserved internal viral proteins, like M1, NP, PA and PB2. Therefore, CTLs display a high degree of cross-reactivity with influenza A viruses of various subtypes. T cell receptor (TCR) activation by a specific epitope-MHC class I complex results in a lytic response, mediated by the release of perforin and granzymes causing apoptosis of the infected cell. Furthermore, proinflammatory cytokines are produced, like TNF-α, which also inhibit virus replication and enhance lytic activity. Also, FasL expression is upregulated which promotes apoptosis of infected cells. After infection, a pool of long-lived antigen-specific central memory and effector memory CD8+ T cells is formed, which form the basis for more rapid and stronger recall responses upon secondary infections.

27Much of the current knowledge about the protective role of CD8+ T cells in influenza A virus infections has been obtained from mouse studies which showed that CD8+ T cells contribute to homo- and heterosubtypic immunity. Evidence that CTLs protect against influenza in humans is sparse. A recent study indicated the presence of heterosubtypic memory CD4+ and CD8+ T cells against the 2009 pandemic H1N1 virus in naïve individuals. It was shown that the extent of lytic activity of PBMC inversely correlated with the extent of virus shedding after experimental infection of subjects that lacked antibodies to the life-attenuated strain used for infection. More circumstantial evidence for a protective role of CD8+ T cells in heterosubtypic influenza infections in humans stems from epidemiological studies. People who had a symptomatic influenza A infection with the H1N1 strain prior to the 1957 pandemic were partially protected from infection with the pandemic H2N2 strain. A similar trend was found in isolated infections with the H5N1.

3.2.3. Regulatory T Cells and Th17 Cells

28In addition to the activation of virus-specific CD4+ T cells and CD8+ T cells, two other cell types are activated, namely forkhead box P3 (FOXP3)+ regulatory T cells (Tregs) and T helper 17 cells (Th17). Tregs play an important role in balancing the immune response during infection. They control CD4+ T helper cell and CTL responses in order to prevent immunopathology of infected tissues. Th17 cells produce IL-6 which inhibits the effects of Tregs and therefore promote T helper responses. Furthermore, Th17 have a role during influenza infections in counteracting secondary bacterial infections, e.g., S. aureus pneumonia. Influenza A virus infections may promote secondary bacterial pneumonia by suppressing Th17 cells in an type I IFN-dependent manner.

4. Evasion of the Antiviral Immune Response by Influenza Viruses

29Immune pressure on influenza A viruses forces them to adopt strategies to evade immunity. Binding of influenza viral proteins to various components of the innate immune system leads to their inhibition (Figure 2 and Figure 3), whereas a combination of immune pressure in the human population and the high mutation rate of the influenza A virus leads to the generation of new virus strains that escape the existing adaptive humoral and cellular immune responses (Figure 1 and Figure 5).

4.1. Escape from Innate Immunity

30Influenza A viruses have adopted various strategies to evade the antiviral nature of the innate immune system.

31In particular, the NS1 protein contributes to antagonizing the antiviral innate immune response. Cells infected with genetically modified influenza viruses with a non-functional NS1 gene displayed stronger IFN responses than cells infected with wild type virus. Viruses with a NS1 defect also display reduced virulence after infection of mice and pigs. NS1 inhibits RIG-I receptor signaling by various means. The NS1 protein blocks the recognition of 5'-phosphorylated viral ssRNA by the RIG-I receptor. More downstream of the RIG-I signaling pathway, NS1 prevents oligomerization of TRIM25 by interacting with the coiled coil domain, and so inhibits TRIM25-mediated RIG-I CARD ubiquitination which is essential for downstream signaling. Finally, activation and nuclear translocation of IRF-3, NF-κB and ATF-2/c-Jun is also prevented by NS1. Hereby NS1 limits RIG-I mediated transcriptional activation of the IFN-β promoter. NS1 also alters host cell gene expression by binding to CPSF30 (cleavage and polyadenylation specificity factor); it prevents polyadenylation of the 3' end of host pre-mRNA. Furthermore, NS1 limits gene expression in general, interfering with the mRNA export machinery.

32NS1 is not the only viral protein that restrains the innate immune system. Both influenza PB2 (especially variants containing an aspartic acid at position 9) and PB1-F2 (only variants containing a serine at position 66) limit the production of IFN-β through association with MAVS.

33Viral proteins PB2, PB1 and PA form the influenza polymerase complex, the main function of which is viral RNA and mRNA synthesis. In addition, it is also involved in cap-snatching of host mRNAs and thereby reduces host cell gene expression including that of IFN-β.

34The recently discovered PA-X viral protein is able to repress cellular gene expression, especially those genes involved in regulating the initiation of the cellular immune response.

35As described above, influenza A virus infection leads to the production of antiviral PKR (Table 1). In order for PKR to limit viral replication, it first needs to be activated by viral dsRNA. PKR activation is under tight regulation of the cellular p58IPK protein which inhibits PKR activity, but is inactive when it forms a complex with heatshock protein 40 (hsp40). Binding of NP to the p58IPK-hsp40 complex releases p58IPK, and thereby NP inhibits the effects of PKR. In contrast, the influenza M2 protein, which also binds the p58IPK-hsp40 complex, inhibits p58IPK release and thereby limits protein synthesis which eventually leads to host cell apoptosis, possibly enhancing viral particle release.

36By encapsidating influenza A viral RNA, the NP protein is likely to reduce the formation of dsRNA, which could otherwise lead to activation of RIG-I signaling. Since most PRRs are located inside the cytoplasm, the nuclear replication strategy of the influenza A virus also prevents the recognition of viral RNA by cytosolic PRR.

37In addition to limiting the production of type I IFNs, influenza A virus also disturbs type I IFN receptor signaling. Influenza A virus infection induces the expression of SOCS (suppressor of cytokine signaling) proteins which inhibit IFN α/β receptor signaling on the level of JAK/STAT activation.

38Besides interfering with innate signaling, influenza A viruses are also able to counteract cells of the innate immune system. For example, influenza virus infection of monocytes impairs their ability to differentiate into mature DCs. Furthermore, it was shown that NS1 can inhibit DC maturation, and so indirectly limit the induction of virus-specific CD8+ T cell responses. The NK response elicited during an infection is also evaded by the influenza A virus. The gradual mutation of glycosylation sites of influenza virus HA proteins leads to reduced NK recognition of the HA on virus-infected cells. Downregulation of the ζ chain of NKp46 receptors by free HA proteins results in impaired signaling and thereby decreased cytotoxicity of NK cells. Furthermore, influenza A virus can directly infect and kill NK cells.

4.2. Escaping the Humoral Immune Response

39Various mechanisms contribute to immune evasion of influenza A viruses from the humoral immune response. Due to the lack of proofreading activity, the transcription of viral RNA by the viral RNA polymerase is error prone and results in mis-incorporation of nucleotides. As a result, quasi species of viruses are formed with random mutations in the genome. Under the selective pressure of antibodies that are present in the human population, induced after influenza virus infections and/or vaccination, variants are positively selected from the quasi species that have accumulated amino acid substitutions in the antigenic sites of HA that are recognized by virus-neutralizing antibodies. This phenomenon is known as antigenic drift and allows the virus to evade recognition by antibodies and to cause recurrent influenza epidemics yearly (Figure 1).

40Introduction of influenza A viruses of a novel antigenically distinct subtype into the human population is known as antigenic shift and may cause a pandemic outbreak, since neutralizing antibodies against the new virus strain are absent in the population at large (Figure 1). Introduction of antigenically distinct viruses can occur after zoonotic transmission. However, in most cases, pandemics were caused by viruses that had exchanged gene segments between human and avian or swine influenza A viruses. For re-assortment to take place, cells need to be infected with two influenza A viruses simultaneously. Since epithelial cells of the swine respiratory tract have receptors for both avian and human influenza A viruses, this species can serve as a mixing vessel for the emergence of re-assorted influenza A viruses. The 1957 A/H2N2 pandemic was caused after re-assortment of human and avian influenza viruses, as was the 1968 A/H3N2 pandemic virus. The virus that caused the 2009 A/H1N1 pandemic emerged after multiple re-assortment events between avian, swine and human influenza A viruses. The emergence of the 2009 pandemic strain highlights the importance of pigs as mixing vessels for influenza A viruses. A recent study suggests that besides the pig, the quail could also serve as a mixing vessel for emerging re-assorted influenza A viruses.

41Of interest, functionally important and conserved sequences in the surface proteins, like the fusion peptide, are inaccessible for antibody recognition, since they are buried inside the protein. Similar strategies to evade antibody recognition are shared by other viruses, like human immunodeficiency virus (HIV).

4.3. Escaping the Cellular Immune Response

42Viruses have adopted various strategies to evade recognition by virus-specific T cells. For example, viruses with a large DNA genome (e.g., herpes viruses) can encode proteins that interfere with various steps in the antigen processing and presentation pathways. Most RNA viruses, including influenza viruses, have relatively small genomes and limited coding capacity. However, they can evade recognition by T cells through their high mutation rates and the selective pressure exerted by virus‑specific T cells.

43Relatively more non-synonymous mutations are observed in the CTL epitope regions of influenza virus NP than in the rest of the protein, indicating that CTL epitopes are under selective pressure. However, mutations flanking CTL epitopes may also affect the liberation of antigenic peptides from the protein by the proteasome or transport by TAP into the ER (Figure 5), as was demonstrated for HIV.

44Amino acid substitutions inside CTL epitopes may affect presentation of the epitope in different ways. Amino acid substitutions at an anchor residue may result in complete loss of the epitope, since it may no longer bind to its corresponding MHC class I molecule (Figure 5). Mutations at TCR contact residues can affect recognition by specific T cells, since the epitope no longer matches the specificity of the TCR (Figure 5). These types of mutations have been observed in escape mutants of viruses that chronically infect their host, like HIV-1. Both types of amino acid substitutions also have been observed during the evolution of seasonal A/H3N2 influenza viruses. An example of a mutation at an anchor residue is the R384G substitution in the HLA‑B*2705 restricted NP383-391 epitope. This substitution considerably affected the human virus-specific CTL response in vitro. It is remarkable that this mutation reached fixation rapidly, despite the fact that it is recognized by a minority of human subjects only. This could be explained by strong intra-host advantages and founder effects in a theoretical model.

45An example of amino acid variation at TCR residues includes that observed in the HLA-B*3501 restricted NP418-426 epitope. Variation in this epitope displays signs of antigenic drift, and dictates the specificity of the CTL response to this epitope and also forms an explanation for cross‑reactivity of CTL against contemporary viruses with historic strains. Of interest, functional constraints may limit variation in CTL. For example, the M158-66 epitope from the matrix protein is highly conserved, despite its immunodominant nature and its restriction by HLA-A*0201, which has a high prevalence in the human population. Influenza viruses do not tolerate mutations in this epitope without loss of viral fitness.

46The R384G mutation in the NP383-391 epitope was also detrimental to viral fitness and was only tolerated in the presence of functionally compensatory co-mutations. At present, it is unknown if influenza viruses can also accumulate mutations flanking CTL epitopes in order to prevent efficient processing and presentation of these epitopes. Of interest, amino acid variation in the HA of influenza A/H3N2 viruses was also associated with escape from recognition by CD4+ T cells, but not with escape from recognition by antibodies.

5.1. Current Influenza Vaccines

47Currently used seasonal influenza vaccines are predominantly inactivated vaccine preparations. Their use aims at the induction of strain-specific antibodies that match the epidemic strains. Although these vaccines are considered safe and efficacious, they also have some drawbacks that are addressed by new vaccine technologies. As described above, antigenic drift of influenza viruses allows the seasonal viruses to escape the neutralizing activity of antibodies induced by previous infections or vaccination. Therefore, the vaccine fails to afford life-long protection and needs to be updated almost annually. Furthermore, the production of the vaccine takes several months, so the recommendation for the vaccine strains of the upcoming influenza season is made months in advance. In most influenza seasons, the predicted vaccine strains match the epidemic strains. Occasionally however, a predicted influenza vaccine strain does not match the circulating strain, resulting in suboptimal protection afforded by the vaccine. In the event of an emerging pandemic outbreak, the time needed to produce and distribute a pandemic influenza vaccine is also a major drawback. Seasonal influenza vaccines do not afford protection against pandemic strains of novel subtypes, since the vaccine-induced antibodies do not cross-react and cross-reactive CD8+ T cell responses are induced inefficiently.

48Alternatively, cold-adapted live-attenuated seasonal influenza vaccines are used. The advantage of live-attenuated vaccines is that they also elicit cellular immune responses and mucosal immunity. More recently, live-attenuated influenza vaccines have been developed by disrupting NS1 activity through deletion or truncation of the NS1 gene. Hence, the virus is unable to interfere with the innate immune response.

5.2. Novel Vaccines

49Ideally, seasonal vaccines are used that induce broad-protective immunity against drift variants and potentially pandemic viruses of novel subtypes. Currently-used inactivated vaccines may even interfere with the induction of cell-mediated immunity otherwise induced by natural infections, especially in young children that are still immunologically naïve to influenza viruses. In this way, inactivated vaccines can hamper the development of heterosubtypic immunity. Thus, the development of vaccines that induce broadly neutralizing antibodies and preferably long-lasting heterosubtypic CTL responses is desirable.

50Since viral proteins like NP and M1 are highly conserved, they are likely targets for the induction of cross-reactive T cell responses. Induction of efficient CTL responses depends on effective endogenous antigen processing and presentation by MHC class I. This requires effective delivery of viral proteins into the cytosol. Several cytosolic delivery vaccine candidates are now under investigation, including DNA vaccines, recombinant viral vectors, ISCOMS and virosomes, some of which already have made it into clinical trials. Also, the induction of cross-reactive antibodies has attracted attention in recent years; antibodies directed against the more conserved stem region of the HA molecule are of especial interest. In contrast to the subtype-specific antibodies induced against the globular head of HA, these HA stem-specific antibodies display broad-neutralizing activity against multiple influenza virus subtypes. Using this stem region as an immunogen, broadly protective antibody responses could be induced.

51Also, the ectodomain of the M2 protein is highly conserved and antibodies induced against this region afford protection against challenge infection. The mode of action is not neutralization per se, since M2 is a minor antigen on virus particles. However, since it is also expressed on the surface of infected cells, ADCC is probably responsible for the protective effect of these antibodies.

52Thus, vaccines that induce both humoral and cell-mediated immune responses directed to conserved regions of influenza A virus, in addition to strain-specific antibodies, are likely to afford protective immunity to a large variety of influenza A viruses, including drift variants and viruses of novel subtypes.

6. Concluding Remarks

53Our knowledge of the complexity of interaction between host immune responses and variable pathogens, like influenza viruses, has increased tremendously. Insight has been obtained on how influenza A viruses evade recognition by components of the immune system. Although these insights have helped us to decrease both morbidity and mortality, mainly by developing effective seasonal vaccines, there are still gaps in our understanding that provide room for improvement for the development of more broadly protective vaccines. The induction of CTL responses to conserved epitopes, preferably those that are under functional constraints, may be a venue to develop broadly protective vaccines. Current research also focuses on cross-neutralizing antibody responses directed to more conserved regions of the surface proteins. If these regions are also under functional constraints, vaccines aimed at the induction of antibodies against these regions would suffer to a lesser extent in terms of variability in the target region.

54Collectively, the new developments may counteract the variable nature of influenza viruses and yield vaccines that afford protection against both seasonal influenza viruses and future pandemic strains.

References 330

1.
Palese P., Shaw M.L. Orthomyxoviridae: The viruses and their replication. Fields Virology. 2007;2:1647-1689.
Not in our library
2.
Influenza (seasonal) fact sheet No 211.
Not in our library
3.
Stohr K. Influenza—WHO cares. Lancet Infect. Dis. 2002;2:517.
Not in our library10.1016/s1473-3099(02)00366-3
4.
Jagger B.W., Wise H.M., Kash J.C., Walters K.A., Wills N.M., Xiao Y.L., Dunfee R.L., Schwartzman L.M., Ozinsky A., Bell G.L., et al. An overlapping protein-coding region in influenza a virus segment 3 modulates the host response. Science. 2012;337:199-204.
Not in our library10.1126/science.1222213
5.
Fouchier R.A., Munster V., Wallensten A., Bestebroer T.M., Herfst S., Smith D., Rimmelzwaan G.F., Olsen B., Osterhaus A.D. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J. Virol. 2005;79:2814-2822.
Not in our library10.1128/jvi.79.5.2814-2822.2005
6.
A revision of the system of nomenclature for influenza viruses: A WHO memorandum. Bull World Health Organ. 1980;58:585-591.
Not in our library
7.
Tong S., Li Y., Rivailler P., Conrardy C., Castillo D.A., Chen L.M., Recuenco S., Ellison J.A., Davis C.T., York I.A., et al. A distinct lineage of influenza A virus from bats. Proc. Natl. Acad. Sci. U. S. A. 2012;109:4269-4274.
Not in our library10.1073/pnas.1116200109
8.
Smith D.J., Lapedes A.S., de Jong J.C., Bestebroer T.M., Rimmelzwaan G.F., Osterhaus A.D., Fouchier R.A. Mapping the antigenic and genetic evolution of influenza virus. Science. 2004;305:371-376.
Not in our library10.1126/science.1097211
9.
Herfst S., Schrauwen E.J.A., Linster M., Chutinimitkul S., de Wit E., Munster V.J., Sorrell E.M., Bestebroer T.M., Burke D.F., Smith D.J., et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science. 2012;336:1534-1541.
Not in our library10.1126/science.1213362
10.
De Jong J.C., Rimmelzwaan G.F., Fouchier R.A., Osterhaus A.D. Influenza virus: A master of metamorphosis. J. Infect. 2000;40:218-228.
Not in our library10.1053/jinf.2000.0652
11.
Johnson N.P., Mueller J. Updating the accounts: Global mortality of the 1918-1920 "Spanish" influenza pandemic. Bull. Hist. Med. 2002;76:105-115.
Not in our library10.1353/bhm.2002.0022
12.
Garten R.J., Davis C.T., Russell C.A., Shu B., Lindstrom S., Balish A., Sessions W.M., Xu X., Skepner E., Deyde V., et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009;325:197-201.
Not in our library10.1126/science.1176225
13.
de Wit E., Kawaoka Y., de Jong M.D., Fouchier R.A. Pathogenicity of highly pathogenic avian influenza virus in mammals. Vaccine. 2008;26:D54-D58.
Not in our library10.1016/j.vaccine.2008.07.072
14.
Kuiken T., Holmes E.C., McCauley J., Rimmelzwaan G.F., Williams C.S., Grenfell B.T. Host species barriers to influenza virus infections. Science. 2006;312:394-397.
Not in our library10.1126/science.1122818
15.
Avian-to-human transmission of H9N2 subtype influenza A viruses: Relationship between H9N2 and H5N1 human isolates · 2000
Not checked
16.
Fouchier R.A., Schneeberger P.M., Rozendaal F.W., Broekman J.M., Kemink S.A., Munster V., Kuiken T., Rimmelzwaan G.F., Schutten M., Van Doornum G.J., et al. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc. Natl. Acad. Sci. U. S. A. 2004;101:1356-1361.
Not in our library10.1073/pnas.0308352100
17.
Koopmans M., Wilbrink B., Conyn M., Natrop G., van der Nat H., Vennema H., Meijer A., van Steenbergen J., Fouchier R., Osterhaus A., et al. Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet. 2004;363:587-593.
Not in our library10.1016/s0140-6736(04)15589-x
18.
de Jong J.C., Claas E.C., Osterhaus A.D., Webster R.G., Lim W.L. A pandemic warning? Nature. 1997;389:554.
Not in our library10.1038/39218
19.
de Jong M.D., Bach V.C., Phan T.Q., Vo M.H., Tran T.T., Nguyen B.H., Beld M., Le T.P., Truong H.K., Nguyen V.V., et al. Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. New Engl. J. Med. 2005;352:686-691.
Not in our library10.1056/nejmoa044307
20.
Gambotto A., Barratt-Boyes S.M., de Jong M.D., Neumann G., Kawaoka Y. Human infection with highly pathogenic H5N1 influenza virus. Lancet. 2008;371:1464-1475.
Not in our library10.1016/s0140-6736(08)60627-3
21.
Abdel-Ghafar A.N., Chotpitayasunondh T., Gao Z., Hayden F.G., Nguyen D.H., de Jong M.D., Naghdaliyev A., Peiris J.S., Shindo N., Soeroso S., et al. Update on avian influenza A (H5N1) virus infection in humans. New Engl. J. Med. 2008;358:261-273.
Not in our library10.1056/nejmra0707279
22.
Beigel J.H., Farrar J., Han A.M., Hayden F.G., Hyer R., de Jong M.D., Lochindarat S., Nguyen T.K., Nguyen T.H., Tran T.H., et al. Avian influenza A (H5N1) infection in humans. New Engl. J. Med. 2005;353:1374-1385.
Not in our library10.1056/nejmra052211
23.
WHO. Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO, 2003-2012.
Not in our library
24.
Wang T.T., Parides M.K., Palese P. Seroevidence for H5N1 influenza infections in humans: Meta-analysis. Science. 2012;335:1463.
Not in our library10.1126/science.1218888
25.
Kandun I.N., Wibisono H., Sedyaningsih E.R., Yusharmen, Hadisoedarsuno W., Purba W., Santoso H., Septiawati C., Tresnaningsih E., Heriyanto B., et al. Three Indonesian clusters of H5N1 virus infection in 2005. New Engl. J. Med. 2006;355:2186-2194.
Not in our library10.1056/nejmoa060930
26.
Ungchusak K., Auewarakul P., Dowell S.F., Kitphati R., Auwanit W., Puthavathana P., Uiprasertkul M., Boonnak K., Pittayawonganon C., Cox N.J., et al. Probable person-to-person transmission of avian influenza A (H5N1). New Engl. J. Med. 2005;352:333-340.
Not in our library10.1056/nejmoa044021
27.
Wang H., Feng Z., Shu Y., Yu H., Zhou L., Zu R., Huai Y., Dong J., Bao C., Wen L., et al. Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China. Lancet. 2008;371:1427-1434.
Not in our library10.1016/s0140-6736(08)60493-6
28.
Imai M., Watanabe T., Hatta M., Das S.C., Ozawa M., Shinya K., Zhong G., Hanson A., Katsura H., Watanabe S., et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature. 2012;486:420-428.
Not in our library10.1038/nature10831
29.
Russell C.A., Fonville J.M., Brown A.E.X., Burke D.F., Smith D.L., James S.L., Herfst S., van Boheemen S., Linster M., Schrauwen E.J., et al. The potential for respiratory droplet transmissible A/H5N1 influenza virus to evolve in a mammalian host. Science. 2012;336:1541-1547.
Not in our library10.1126/science.1222526
30.
Holt P.G., Strickland D.H., Wikstrom M.E., Jahnsen F.L. Regulation of immunological homeostasis in the respiratory tract. Nat. Rev. 2008;8:142-152.
Not in our library10.1038/nri2236
31.
Sanders C.J., Doherty P.C., Thomas P.G. Respiratory epithelial cells in innate immunity to influenza virus infection. Cell Tissue Res. 2011;343:13-21.
Not in our library10.1007/s00441-010-1043-z
32.
Blasius A.L., Beutler B. Intracellular toll-like receptors. Immunity. 2010;32:305-315.
Not in our library10.1016/j.immuni.2010.03.012
33.
Pang I.K., Iwasaki A. Inflammasomes as mediators of immunity against influenza virus. Trends Immunol. 2011;32:34-41.
Not in our library10.1016/j.it.2010.11.004
34.
Takeuchi O., Akira S. Innate immunity to virus infection. Immunol. Rev. 2009;227:75-86.
Not in our library10.1111/j.1600-065x.2008.00737.x
35.
Lund J.M., Alexopoulou L., Sato A., Karow M., Adams N.C., Gale N.W., Iwasaki A., Flavell R.A. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc. Natl. Acad. Sci. U. S. A. 2004;101:5598-5603.
Not in our library10.1073/pnas.0400937101
36.
Diebold S.S., Kaisho T., Hemmi H., Akira S., Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 2004;303:1529-1531.
Not in our library10.1126/science.1093616
37.
Guillot L., Le Goffic R., Bloch S., Escriou N., Akira S., Chignard M., Si-Tahar M. Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J. Biol. Chem. 2005;280:5571-5580.
Not in our library10.1074/jbc.m410592200
38.
Imai Y., Kuba K., Neely G.G., Yaghubian-Malhami R., Perkmann T., van Loo G., Ermolaeva M., Veldhuizen R., Leung Y.H., Wang H., et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008;133:235-249.
Not in our library10.1016/j.cell.2008.02.043
39.
Kurt-Jones E.A., Popova L., Kwinn L., Haynes L.M., Jones L.P., Tripp R.A., Walsh E.E., Freeman M.W., Golenbock D.T., Anderson L.J., et al. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat. Immunol. 2000;1:398-401.
Not in our library10.1038/80833
40.
Hashimoto Y., Moki T., Takizawa T., Shiratsuchi A., Nakanishi Y. Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice. J. Immunol. 2007;178:2448-2457.
Not in our library10.4049/jimmunol.178.4.2448
41.
Hornung V., Ellegast J., Kim S., Brzozka K., Jung A., Kato H., Poeck H., Akira S., Conzelmann K.K., Schlee M., et al. 5'-Triphosphate RNA is the ligand for RIG-I. Science. 2006;314:994-997.
Not in our library10.1126/science.1132505
42.
Pichlmair A., Schulz O., Tan C.P., Naslund T.I., Liljestrom P., Weber F., Reis e Sousa C. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates. Science. 2006;314:997-1001.
Not in our library10.1126/science.1132998
43.
Kato H., Takeuchi O., Sato S., Yoneyama M., Yamamoto M., Matsui K., Uematsu S., Jung A., Kawai T., Ishii K.J., et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006;441:101-105.
Not in our library10.1038/nature04734
44.
Loo Y.M., Gale M. Immune signaling by RIG-I-like receptors. Immunity. 2011;34:680-692.
Not in our library10.1016/j.immuni.2011.05.003
45.
Kanneganti T.D., Body-Malapel M., Amer A., Park J.H., Whitfield J., Franchi L., Taraporewala Z.F., Miller D., Patton J.T., Inohara N., et al. Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J. Biol. Chem. 2006;281:36560-36568.
Not in our library10.1074/jbc.m607594200
46.
Gack M.U., Shin Y.C., Joo C.H., Urano T., Liang C., Sun L., Takeuchi O., Akira S., Chen Z., Inoue S., et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature. 2007;446:916-920.
Not in our library10.1038/nature05732
47.
Kawai T., Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34:637-650.
Not in our library10.1016/j.immuni.2011.05.006
48.
Hale B.G., Albrecht R.A., Garcia-Sastre A. Innate immune evasion strategies of influenza viruses. Future Microbiol. 2010;5:23-41.
Not in our library10.2217/fmb.09.108
49.
Randall R.E., Goodbourn S. Interferons and viruses: An interplay between induction, signalling, antiviral responses and virus countermeasure. J. Gen. Virol. 2008;89:1-47.
Not in our library10.1099/vir.0.83391-0
50.
Chelbi-Alix M.K., Wietzerbin J. Interferon, a growing cytokine family: 50 years of interferon research. Biochimie. 2007;89:713-718.
Not in our library10.1016/j.biochi.2007.05.001
51.
Van Hoeven N., Belser J.A., Szretter K.J., Zeng H., Staeheli P., Swayne D.E., Katz J.M., Tumpey T.M. Pathogenesis of 1918 pandemic and H5N1 influenza virus infections in a guinea pig model: Antiviral potential of exogenous alpha interferon to reduce virus shedding. J. Virol. 2009;83:2851-2861.
Not in our library10.1128/jvi.02174-08
52.
Szretter K.J., Gangappa S., Belser J.A., Zeng H., Chen H., Matsuoka Y., Sambhara S., Swayne D.E., Tumpey T.M., Katz J.M. Early control of H5N1 influenza virus replication by the type I interferon response in mice. J. Virol. 2009;83:5825-5834.
Not in our library10.1128/jvi.02144-08
53.
Sato M., Hata N., Asagiri M., Nakaya T., Taniguchi T., Tanaka N. Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7. FEBS Lett. 1998;441:106-110.
Not in our library10.1016/s0014-5793(98)01514-2
54.
von der Malsburg A., Abutbul-Ionita I., Haller O., Kochs G., Danino D. Stalk domain of the dynamin-like MxA GTPase protein mediates membrane binding and liposome tubulation via the unstructured L4 loop. J. Biol. Chem. 2011;286:37858-37865.
Not in our library10.1074/jbc.m111.249037
55.
Haller O., Gao S., von der Malsburg A., Daumke O., Kochs G. Dynamin-like MxA GTPase: Structural insights into oligomerization and implications for antiviral activity. J. Biol. Chem. 2010;285:28419-28424.
Not in our library10.1074/jbc.r110.145839
56.
Haller O., Kochs G. Interferon-induced mx proteins: Dynamin-like GTPases with antiviral activity. Traffic. 2002;3:710-717.
Not in our library10.1034/j.1600-0854.2002.31003.x
57.
Pindel A., Sadler A. The role of protein kinase R in the interferon response. J. Interferon Cytokine Res. 2011;31:59-70.
Not in our library10.1089/jir.2010.0099
58.
Garcia M.A., Gil J., Ventoso I., Guerra S., Domingo E., Rivas C., Esteban M. Impact of protein kinase PKR in cell biology: From antiviral to antiproliferative action. Microbiol. Mol. Biol. Rev. 2006;70:1032-1060.
Not in our library10.1128/mmbr.00027-06
59.
Chakrabarti A., Jha B.K., Silverman R.H. New insights into the role of RNase L in innate immunity. J. Interferon Cytokine Res. 2011;31:49-57.
Not in our library10.1089/jir.2010.0120
60.
Silverman R.H. Viral encounters with 2',5'-oligoadenylate synthetase and RNase L during the interferon antiviral response. J. Virol. 2007;81:12720-12729.
Not in our library10.1128/jvi.01471-07
61.
Lenschow D.J., Lai C., Frias-Staheli N., Giannakopoulos N.V., Lutz A., Wolff T., Osiak A., Levine B., Schmidt R.E., Garcia-Sastre A., et al. IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. Proc. Natl. Acad. Sci. U. S. A. 2007;104:1371-1376.
Not in our library10.1073/pnas.0607038104
62.
Wang X., Hinson E.R., Cresswell P. The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts. Cell Host Microbe. 2007;2:96-105.
Not in our library10.1016/j.chom.2007.06.009
63.
Watanabe R., Leser G.P., Lamb R.A. Influenza virus is not restricted by tetherin whereas influenza VLP production is restricted by tetherin. Virology. 2011;417:50-56.
Not in our library10.1016/j.virol.2011.05.006
64.
Yondola M.A., Fernandes F., Belicha-Villanueva A., Uccelini M., Gao Q., Carter C., Palese P. Budding capability of the influenza virus neuraminidase can be modulated by tetherin. J. Virol. 2011;85:2480-2491.
Not in our library10.1128/jvi.02188-10
65.
Brass A.L., Huang I.C., Benita Y., John S.P., Krishnan M.N., Feeley E.M., Ryan B.J., Weyer J.L., van der Weyden L., Fikrig E., et al. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell. 2009;139:1243-1254.
Not in our library10.1016/j.cell.2009.12.017
66.
Turner S.J., Olivas E., Gutierrez A., Diaz G., Doherty P.C. Disregulated influenza A virus-specific CD8+ T cell homeostasis in the absence of IFN-gamma signaling. J. Immunol. 2007;178:7616-7622.
Not in our library10.4049/jimmunol.178.12.7616
67.
Bot A., Bot S., Bona C.A. Protective role of gamma interferon during the recall response to influenza virus. J. Virol. 1998;72:6637-6645.
Not in our library10.1128/jvi.72.8.6637-6645.1998
68.
Interferon-λ Contributes to Innate Immunity of Mice against Influenza A Virus but Not against Hepatotropic Viruses · 2008
No notice
69.
McGill J., Heusel J.W., Legge K.L. Innate immune control and regulation of influenza virus infections. J. Leukoc. Biol. 2009;86:803-812.
Not in our library10.1189/jlb.0509368
70.
Snelgrove R.J., Goulding J., Didierlaurent A.M., Lyonga D., Vekaria S., Edwards L., Gwyer E., Sedgwick J.D., Barclay A.N., Hussell T. A critical function for CD200 in lung immune homeostasis and the severity of influenza infection. Nat. Immunol. 2008;9:1074-1083.
Not in our library10.1038/ni.1637
71.
Lin K.L., Suzuki Y., Nakano H., Ramsburg E., Gunn M.D. CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. J. Immunol. 2008;180:2562-2572.
Not in our library10.4049/jimmunol.180.4.2562
72.
Dawson T.C., Beck M.A., Kuziel W.A., Henderson F., Maeda N. Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus. Am. J. Pathol. 2000;156:1951-1959.
Not in our library10.1016/s0002-9440(10)65068-7
73.
Herold S., von Wulffen W., Steinmueller M., Pleschka S., Kuziel W.A., Mack M., Srivastava M., Seeger W., Maus U.A., Lohmeyer J. Alveolar epithelial cells direct monocyte transepithelial migration upon influenza virus infection: Impact of chemokines and adhesion molecules. J. Immunol. 2006;177:1817-1824.
Not in our library10.4049/jimmunol.177.3.1817
74.
van Riel D., Leijten L.M., van der Eerden M., Hoogsteden H.C., Boven L.A., Lambrecht B.N., Osterhaus A.D., Kuiken T. Highly pathogenic avian influenza virus H5N1 infects alveolar macrophages without virus production or excessive TNF-alpha induction. PLoS Pathog. 2011;7:e1002099.
Not in our library10.1371/journal.ppat.1002099
75.
Becker S., Quay J., Soukup J. Cytokine (tumor necrosis factor, IL-6, and IL-8) production by respiratory syncytial virus-infected human alveolar macrophage. J. Immunol. 1991;147:4307-4312.
Not in our library
76.
Tumpey T.M., Garcia-Sastre A., Taubenberger J.K., Palese P., Swayne D.E., Pantin-Jackwood M.J., Schultz-Cherry S., Solorzano A., van Rooijen N., Katz J.M., et al. Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: Functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. J. Virol. 2005;79:14933-14944.
Not in our library10.1128/jvi.79.23.14933-14944.2005
77.
Kim H.M., Lee Y.W., Lee K.J., Kim H.S., Cho S.W., van Rooijen N., Guan Y., Seo S.H. Alveolar macrophages are indispensable for controlling influenza viruses in lungs of pigs. J. Virol. 2008;82:4265-4274.
Not in our library10.1128/jvi.02602-07
78.
Huber V.C., Lynch J.M., Bucher D.J., Le J., Metzger D.W. Fc receptor-mediated phagocytosis makes a significant contribution to clearance of influenza virus infections. J. Immunol. 2001;166:7381-7388.
Not in our library10.4049/jimmunol.166.12.7381
79.
Jayasekera J.P., Vinuesa C.G., Karupiah G., King N.J. Enhanced antiviral antibody secretion and attenuated immunopathology during influenza virus infection in nitric oxide synthase-2-deficient mice. J. Gen. Virol. 2006;87:3361-3371.
Not in our library10.1099/vir.0.82131-0
80.
Peper R.L., van Campen H. Tumor necrosis factor as a mediator of inflammation in influenza A viral pneumonia. Microb. Pathog. 1995;19:175-183.
Not in our library10.1006/mpat.1995.0056
81.
Mendelson M., Tekoah Y., Zilka A., Gershoni-Yahalom O., Gazit R., Achdout H., Bovin N.V., Meningher T., Mandelboim M., Mandelboim O., et al. NKp46 O-glycan sequences that are involved in the interaction with hemagglutinin type 1 of influenza virus. J. Virol. 2010;84:3789-3797.
Not in our library10.1128/jvi.01815-09
82.
Arnon T.I., Lev M., Katz G., Chernobrov Y., Porgador A., Mandelboim O. Recognition of viral hemagglutinins by NKp44 but not by NKp30. Eur. J. Immunol. 2001;31:2680-2689.
Not in our library10.1002/1521-4141(200109)31:9<2680::aid-immu2680>3.0.co;2-a
83.
Mandelboim O., Lieberman N., Lev M., Paul L., Arnon T.I., Bushkin Y., Davis D.M., Strominger J.L., Yewdell J.W., Porgador A. Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature. 2001;409:1055-1060.
Not in our library10.1038/35059110
84.
Gazit R., Gruda R., Elboim M., Arnon T.I., Katz G., Achdout H., Hanna J., Qimron U., Landau G., Greenbaum E., et al. Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1. Nat. Immunol. 2006;7:517-523.
Not in our library10.1038/ni1322
85.
Hashimoto G., Wright P.F., Karzon D.T. Antibody-dependent cell-mediated cytotoxicity against influenza virus-infected cells. J. Infect. Dis. 1983;148:785-794.
Not in our library10.1093/infdis/148.5.785
86.
Sun P.D. Structure and function of natural-killer-cell receptors. Immunol. Res. 2003;27:539-548.
Not in our library10.1385/ir:27:2-3:539
87.
Jegerlehner A., Schmitz N., Storni T., Bachmann M.F. Influenza A vaccine based on the extracellular domain of M2: Weak protection mediated via antibody-dependent NK cell activity. J. Immunol. 2004;172:5598-5605.
Not in our library10.4049/jimmunol.172.9.5598
88.
Banchereau J., Steinman R.M. Dendritic cells and the control of immunity. Nature. 1998;392:245-252.
Not in our library10.1038/32588
89.
Guermonprez P., Valladeau J., Zitvogel L., Thery C., Amigorena S. Antigen presentation and T cell stimulation by dendritic cells. Annu. Rev. Immunol. 2002;20:621-667.
Not in our library10.1146/annurev.immunol.20.100301.064828
90.
GeurtsvanKessel C.H., Lambrecht B.N. Division of labor between dendritic cell subsets of the lung. Mucosal Immunol. 2008;1:442-450.
Not in our library10.1038/mi.2008.39
91.
Bhardwaj N., Bender A., Gonzalez N., Bui L.K., Garrett M.C., Steinman R.M. Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells. J. Clin. Investig. 1994;94:797-807.
Not in our library10.1172/jci117399
92.
Hamilton-Easton A., Eichelberger M. Virus-specific antigen presentation by different subsets of cells from lung and mediastinal lymph node tissues of influenza virus-infected mice. J. Virol. 1995;69:6359-6366.
Not in our library10.1128/jvi.69.10.6359-6366.1995
93.
Yewdell J.W., Reits E., Neefjes J. Making sense of mass destruction: Quantitating MHC class I antigen presentation. Nat. Rev. 2003;3:952-961.
Not in our library10.1038/nri1250
94.
Mori I., Komatsu T., Takeuchi K., Nakakuki K., Sudo M., Kimura Y. In vivo induction of apoptosis by influenza virus. J. Gen. Virol. 1995;76:2869-2873.
Not in our library10.1099/0022-1317-76-11-2869
95.
Braciale T.J., Sun J., Kim T.S. Regulating the adaptive immune response to respiratory virus infection. Nat. Rev. 2012;12:295-305.
Not in our library10.1038/nri3166
96.
Respiratory Dendritic Cell Subsets Differ in Their Capacity to Support the Induction of Virus-Specific Cytotoxic CD8+ T Cell Responses · 2009
No notice
97.
Norbury C.C., Malide D., Gibbs J.S., Bennink J.R., Yewdell J.W. Visualizing priming of virus-specific CD8+ T cells by infected dendritic cells in vivo. Nat. Immunol. 2002;3:265-271.
Not in our library10.1038/ni762
98.
Heer A.K., Harris N.L., Kopf M., Marsland B.J. CD4+ and CD8+ T cells exhibit differential requirements for CCR7-mediated antigen transport during influenza infection. J. Immunol. 2008;181:6984-6994.
Not in our library10.4049/jimmunol.181.10.6984
99.
Legge K.L., Braciale T.J. Accelerated migration of respiratory dendritic cells to the regional lymph nodes is limited to the early phase of pulmonary infection. Immunity. 2003;18:265-277.
Not in our library10.1016/s1074-7613(03)00023-2
100.
Baumgarth N., Herman O.C., Jager G.C., Brown L.E., Herzenberg L.A., Chen J. B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection. J. Exp. Med. 2000;192:271-280.
Not in our library10.1084/jem.192.2.271
101.
Baumgarth N., Tung J.W., Herzenberg L.A. Inherent specificities in natural antibodies: A key to immune defense against pathogen invasion. Springer Semin. Immunopathol. 2005;26:347-362.
Not in our library10.1007/s00281-004-0182-2
102.
Potter C.W., Oxford J.S. Determinants of immunity to influenza infection in man. Br. Med. Bull. 1979;35:69-75.
Not in our library10.1093/oxfordjournals.bmb.a071545
103.
Waffarn E.E., Baumgarth N. Protective B cell responses to flu—No fluke! J. Immunol. 2011;186:3823-3829.
Not in our library10.4049/jimmunol.1002090
104.
de Jong J.C., Palache A.M., Beyer W.E., Rimmelzwaan G.F., Boon A.C., Osterhaus A.D. Haemagglutination-inhibiting antibody to influenza virus. Dev. Biologicals. 2003;115:63-73.
Not in our library
105.
Knossow M., Skehel J.J. Variation and infectivity neutralization in influenza. Immunology. 2006;119:1-7.
Not in our library10.1111/j.1365-2567.2006.02421.x
106.
Wilson I.A., Cox N.J. Structural basis of immune recognition of influenza virus hemagglutinin. Annu. Rev. Immunol. 1990;8:737-771.
Not in our library10.1146/annurev.iy.08.040190.003513
107.
Kilbourne E.D. Influenza as a problem in immunology. J. Immunol. 1978;120:1447-1452.
Not in our library
108.
Potter C.W., Oxford J.S., Shore S.L., McLaren C., Stuart-Harris C. Immunity to influenza in ferrets. I. Response to live and killed virus. Br. J. Exp. Pathol. 1972;53:153-167.
Not in our library
109.
Yu X., Tsibane T., McGraw P.A., House F.S., Keefer C.J., Hicar M.D., Tumpey T.M., Pappas C., Perrone L.A., Martinez O., et al. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature. 2008;455:532-536.
Not in our library10.1038/nature07231
110.
Ikonen N., Strengell M., Kinnunen L., Osterlund P., Pirhonen J., Broman M., Davidkin I., Ziegler T., Julkunen I. High frequency of cross-reacting antibodies against 2009 pandemic influenza A(H1N1) virus among the elderly in Finland. Euro Surveill. 2010;15:pii=19478.
Not in our library
111.
Reed C., Katz J.M. Serological surveys for 2009 pandemic influenza A H1N1. Lancet. 2010;375:1062-1063.
Not in our library10.1016/s0140-6736(09)62194-2
112.
Hancock K., Veguilla V., Lu X., Zhong W., Butler E.N., Sun H., Liu F., Dong L., DeVos J.R., Gargiullo P.M., et al. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. New Engl. J. Med. 2009;361:1945-1952.
Not in our library10.1056/nejmoa0906453
113.
Ekiert D.C., Bhabha G., Elsliger M.A., Friesen R.H., Jongeneelen M., Throsby M., Goudsmit J., Wilson I.A. Antibody recognition of a highly conserved influenza virus epitope. Science. 2009;324:246-251.
Not in our library10.1126/science.1171491
114.
Ekiert D.C., Friesen R.H., Bhabha G., Kwaks T., Jongeneelen M., Yu W., Ophorst C., Cox F., Korse H.J., Brandenburg B., et al. A highly conserved neutralizing epitope on group 2 influenza A viruses. Science. 2011;333:843-850.
Not in our library10.1126/science.1204839
115.
Sui J., Hwang W.C., Perez S., Wei G., Aird D., Chen L.M., Santelli E., Stec B., Cadwell G., Ali M., et al. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat. Struct. Mol. Biol. 2009;16:265-273.
Not in our library10.1038/nsmb.1566
116.
Broadly Protective Monoclonal Antibodies against H3 Influenza Viruses following Sequential Immunization with Different Hemagglutinins · 2010
No notice
117.
Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain · 2010
Not checked
118.
Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells · 2008
No notice
119.
Wang T.T., Tan G.S., Hai R., Pica N., Ngai L., Ekiert D.C., Wilson I.A., Garcia-Sastre A., Moran T.M., Palese P. Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes. Proc. Natl. Acad. Sci. U. S. A. 2010;107:18979-18984.
Not in our library10.1073/pnas.1013387107
120.
Okuno Y., Isegawa Y., Sasao F., Ueda S. A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains. J. Virol. 1993;67:2552-2558.
Not in our library10.1128/jvi.67.5.2552-2558.1993
121.
Bosch B.J., Bodewes R., de Vries R.P., Kreijtz J.H., Bartelink W., van Amerongen G., Rimmelzwaan G.F., de Haan C.A., Osterhaus A.D., Rottier P.J. Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection against pandemic swine-origin 2009 A(H1N1) influenza virus infection in ferrets. J. Virol. 2010;84:10366-10374.
Not in our library10.1128/jvi.01035-10
122.
Johansson B.E., Bucher D.J., Kilbourne E.D. Purified influenza virus hemagglutinin and neuraminidase are equivalent in stimulation of antibody response but induce contrasting types of immunity to infection. J. Virol. 1989;63:1239-1246.
Not in our library10.1128/jvi.63.3.1239-1246.1989
123.
Johansson B.E., Grajower B., Kilbourne E.D. Infection-permissive immunization with influenza virus neuraminidase prevents weight loss in infected mice. Vaccine. 1993;11:1037-1039.
Not in our library10.1016/0264-410x(93)90130-p
124.
Kilbourne E.D., Pokorny B.A., Johansson B., Brett I., Milev Y., Matthews J.T. Protection of mice with recombinant influenza virus neuraminidase. J. Infect. Dis. 2004;189:459-461.
Not in our library10.1086/381123
125.
Schulman J.L., Khakpour M., Kilbourne E.D. Protective effects of specific immunity to viral neuraminidase on influenza virus infection of mice. J. Virol. 1968;2:778-786.
Not in our library10.1128/jvi.2.8.778-786.1968
126.
Treanor J.J., Tierney E.L., Zebedee S.L., Lamb R.A., Murphy B.R. Passively transferred monoclonal antibody to the M2 protein inhibits influenza A virus replication in mice. J. Virol. 1990;64:1375-1377.
Not in our library10.1128/jvi.64.3.1375-1377.1990
127.
Zebedee S.L., Lamb R.A. Influenza A virus M2 protein: Monoclonal antibody restriction of virus growth and detection of M2 in virions. J. Virol. 1988;62:2762-2772.
Not in our library10.1128/jvi.62.8.2762-2772.1988
128.
Mozdzanowska K., Maiese K., Furchner M., Gerhard W. Treatment of influenza virus-infected SCID mice with nonneutralizing antibodies specific for the transmembrane proteins matrix 2 and neuraminidase reduces the pulmonary virus titer but fails to clear the infection. Virology. 1999;254:138-146.
Not in our library10.1006/viro.1998.9534
129.
El Bakkouri K., Descamps F., de Filette M., Smet A., Festjens E., Birkett A., van Rooijen N., Verbeek S., Fiers W., Saelens X. Universal vaccine based on ectodomain of matrix protein 2 of influenza A: Fc receptors and alveolar macrophages mediate protection. J. Immunol. 2011;186:1022-1031.
Not in our library10.4049/jimmunol.0902147
130.
Ebrahimi S.M., Tebianian M. Influenza A viruses: Why focusing on M2e-based universal vaccines. Virus Genes. 2011;42:1-8.
Not in our library10.1007/s11262-010-0547-7
131.
Fiers W., de Filette M., Birkett A., Neirynck S., Min Jou W. A "universal" human influenza A vaccine. Virus Res. 2004;103:173-176.
Not in our library10.1016/j.virusres.2004.02.030
132.
Fiers W., de Filette M., El Bakkouri K., Schepens B., Roose K., Schotsaert M., Birkett A., Saelens X. M2e-based universal influenza A vaccine. Vaccine. 2009;27:6280-6283.
Not in our library10.1016/j.vaccine.2009.07.007
133.
Neirynck S., Deroo T., Saelens X., Vanlandschoot P., Jou W.M., Fiers W. A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat. Med. 1999;5:1157-1163.
Not in our library10.1038/13484
134.
Wang Y., Zhou L., Shi H., Xu H., Yao H., Xi X.G., Toyoda T., Wang X., Wang T. Monoclonal antibody recognizing SLLTEVET epitope of M2 protein potently inhibited the replication of influenza A viruses in MDCK cells. Biochem. Biophys. Res. Comm. 2009;385:118-122.
Not in our library10.1016/j.bbrc.2009.04.129
135.
Fu T.M., Freed D.C., Horton M.S., Fan J., Citron M.P., Joyce J.G., Garsky V.M., Casimiro D.R., Zhao Q., Shiver J.W., et al. Characterizations of four monoclonal antibodies against M2 protein ectodomain of influenza A virus. Virology. 2009;385:218-226.
Not in our library10.1016/j.virol.2008.11.035
136.
Schotsaert M., de Filette M., Fiers W., Saelens X. Universal M2 ectodomain-based influenza A vaccines: Preclinical and clinical developments. Expert Rev. Vaccine. 2009;8:499-508.
Not in our library10.1586/erv.09.6
137.
Matrix Protein 2 Vaccination and Protection against Influenza Viruses, Including Subtype H5N1 · 2007
No notice
138.
Sukeno N., Otsuki Y., Konno J., Yamane N., Odagiri T., Arikawa J., Ishida N. Anti-nucleoprotein antibody response in influenza A infection. Tohoku J. Exp. Med. 1979;128:241-249.
Not in our library10.1620/tjem.128.241
139.
Lamere M.W., Moquin A., Lee F.E., Misra R.S., Blair P.J., Haynes L., Randall T.D., Lund F.E., Kaminski D.A. Regulation of antinucleoprotein IgG by systemic vaccination and its effect on influenza virus clearance. J. Virol. 2011;85:5027-5035.
Not in our library10.1128/jvi.00150-11
140.
Carragher D.M., Kaminski D.A., Moquin A., Hartson L., Randall T.D. A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus. J. Immunol. 2008;181:4168-4176.
Not in our library10.4049/jimmunol.181.6.4168
141.
Bodewes R., Osterhaus A.D., Rimmelzwaan G.F. Targets for the induction of protective immunity against influenza a viruses. Viruses. 2010;2:166-188.
Not in our library10.3390/v2010166
142.
Sambhara S., Kurichh A., Miranda R., Tumpey T., Rowe T., Renshaw M., Arpino R., Tamane A., Kandil A., James O., et al. Heterosubtypic immunity against human influenza A viruses, including recently emerged avian H5 and H9 viruses, induced by FLU-ISCOM vaccine in mice requires both cytotoxic T-lymphocyte and macrophage function. Cell. Immunol. 2001;211:143-153.
Not in our library10.1006/cimm.2001.1835
143.
Rimmelzwaan G.F., Baars M., van Beek R., van Amerongen G., Lovgren-Bengtsson K., Claas E.C., Osterhaus A.D. Induction of protective immunity against influenza virus in a macaque model: Comparison of conventional and iscom vaccines. J. Gen. Virol. 1997;78:757-765.
Not in our library10.1099/0022-1317-78-4-757
144.
Fernandez Gonzalez S., Jayasekera J.P., Carroll M.C. Complement and natural antibody are required in the long-term memory response to influenza virus. Vaccine. 2008;26:I86-I93.
Not in our library10.1016/j.vaccine.2008.11.057
145.
Jayasekera J.P., Moseman E.A., Carroll M.C. Natural antibody and complement mediate neutralization of influenza virus in the absence of prior immunity. J. Virol. 2007;81:3487-3494.
Not in our library10.1128/jvi.02128-06
146.
Voeten J.T., Groen J., van Alphen D., Claas E.C., de Groot R., Osterhaus A.D., Rimmelzwaan G.F. Use of recombinant nucleoproteins in enzyme-linked immunosorbent assays for detection of virus-specific immunoglobulin A (IgA) and IgG antibodies in influenza virus A- or B-infected patients. J. Clin. Microbiol. 1998;36:3527-3531.
Not in our library10.1128/jcm.36.12.3527-3531.1998
147.
Rothbarth P.H., Groen J., Bohnen A.M., de Groot R., Osterhaus A.D. Influenza virus serology—A comparative study. J. Virol. Meth. 1999;78:163-169.
Not in our library10.1016/s0166-0934(98)00174-8
148.
Koutsonanos D.G., del Pilar Martin M., Zarnitsyn V.G., Jacob J., Prausnitz M.R., Compans R.W., Skountzou I. Serological memory and long-term protection to novel H1N1 influenza virus after skin vaccination. J. Infect. Dis. 2011;204:582-591.
Not in our library10.1093/infdis/jir094
149.
Onodera T., Takahashi Y., Yokoi Y., Ato M., Kodama Y., Hachimura S., Kurosaki T., Kobayashi K. Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection. Proc. Natl. Acad. Sci. U. S. A. 2012;109:2485-2490.
Not in our library10.1073/pnas.1115369109
150.
Jones P.D., Ada G.L. Persistence of influenza virus-specific antibody-secreting cells and B-cell memory after primary murine influenza virus infection. Cell. Immunol. 1987;109:53-64.
Not in our library10.1016/0008-8749(87)90291-7
151.
Armstrong S.J., Dimmock N.J. Neutralization of influenza virus by low concentrations of hemagglutinin-specific polymeric immunoglobulin A inhibits viral fusion activity, but activation of the ribonucleoprotein is also inhibited. J. Virol. 1992;66:3823-3832.
Not in our library10.1128/jvi.66.6.3823-3832.1992
152.
Mazanec M.B., Coudret C.L., Fletcher D.R. Intracellular neutralization of influenza virus by immunoglobulin A anti-hemagglutinin monoclonal antibodies. J. Virol. 1995;69:1339-1343.
Not in our library10.1128/jvi.69.2.1339-1343.1995
153.
Zuccotti G., Pogliani L., Pariani E., Amendola A., Zanetti A. Transplacental antibody transfer following maternal immunization with a pandemic 2009 influenza A(H1N1) MF59-adjuvanted vaccine. JAMA. 2010;304:2360-2361.
Not in our library10.1001/jama.2010.1729
154.
Bodewes R., de Mutsert G., van der Klis F.R., Ventresca M., Wilks S., Smith D.J., Koopmans M., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Prevalence of antibodies against seasonal influenza A and B viruses in children in Netherlands. Clin. Vaccine Immunol. 2011;18:469-476.
Not in our library10.1128/cvi.00396-10
155.
Mbawuike I.N., Six H.R., Cate T.R., Couch R.B. Vaccination with inactivated influenza A virus during pregnancy protects neonatal mice against lethal challenge by influenza A viruses representing three subtypes. J. Virol. 1990;64:1370-1374.
Not in our library10.1128/jvi.64.3.1370-1374.1990
156.
Hwang S.D., Shin J.S., Ku K.B., Kim H.S., Cho S.W., Seo S.H. Protection of pregnant mice, fetuses and neonates from lethality of H5N1 influenza viruses by maternal vaccination. Vaccine. 2010;28:2957-2964.
Not in our library10.1016/j.vaccine.2010.02.016
157.
Steinhoff M.C., Omer S.B., Roy E., Arifeen S.E., Raqib R., Altaye M., Breiman R.F., M B.B.S.K. Influenza immunization in pregnancy—Antibody responses in mothers and infants. New Engl. J. Med. 2010;362:1644-1646.
Not in our library10.1056/nejmc0912599
158.
Zhu J., Paul W.E. Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol. Rev. 2010;238:247-262.
Not in our library10.1111/j.1600-065x.2010.00951.x
159.
Lamb J.R., Woody J.N., Hartzman R.J., Eckels D.D. In vitro influenza virus-specific antibody production in man: Antigen-specific and HLA-restricted induction of helper activity mediated by cloned human T lymphocytes. J. Immunol. 1982;129:1465-1470.
Not in our library
160.
Okoye I.S., Wilson M.S. CD4+ T helper 2 cells—Microbial triggers, differentiation requirements and effector functions. Immunology. 2011;134:368-377.
Not in our library10.1111/j.1365-2567.2011.03497.x
161.
Eichelberger M.C., Wang M.L., Allan W., Webster R.G., Doherty P.C. Influenza virus RNA in the lung and lymphoid tissue of immunologically intact and CD4-depleted mice. J. Gen. Virol. 1991;72:1695-1698.
Not in our library10.1099/0022-1317-72-7-1695
162.
Justewicz D.M., Doherty P.C., Webster R.G. The B-cell response in lymphoid tissue of mice immunized with various antigenic forms of the influenza virus hemagglutinin. J. Virol. 1995;69:5414-5421.
Not in our library10.1128/jvi.69.9.5414-5421.1995
163.
Kamperschroer C., Dibble J.P., Meents D.L., Schwartzberg P.L., Swain S.L. SAP is required for Th cell function and for immunity to influenza. J. Immunol. 2006;177:5317-5327.
Not in our library10.4049/jimmunol.177.8.5317
164.
Scherle P.A., Gerhard W. Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin. J. Exp. Med. 1986;164:1114-1128.
Not in our library10.1084/jem.164.4.1114
165.
Schonbeck U., Libby P. The CD40/CD154 receptor/ligand dyad. Cell. Mol. Life Sci. 2001;58:4-43.
Not in our library10.1007/pl00000776
166.
Zhu J., Paul W.E. Heterogeneity and plasticity of T helper cells. Cell Res. 2010;20:4-12.
Not in our library10.1038/cr.2009.138
167.
Mosmann T.R., Cherwinski H., Bond M.W., Giedlin M.A., Coffman R.L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 1986;136:2348-2357.
Not in our library
168.
Belz G.T., Wodarz D., Diaz G., Nowak M.A., Doherty P.C. Compromised influenza virus-specific CD8(+)-T-cell memory in CD4(+)-T-cell-deficient mice. J. Virol. 2002;76:12388-12393.
Not in our library10.1128/jvi.76.23.12388-12393.2002
169.
Deliyannis G., Jackson D.C., Ede N.J., Zeng W., Hourdakis I., Sakabetis E., Brown L.E. Induction of long-term memory CD8(+) T cells for recall of viral clearing responses against influenza virus. J. Virol. 2002;76:4212-4221.
Not in our library10.1128/jvi.76.9.4212-4221.2002
170.
Riberdy J.M., Christensen J.P., Branum K., Doherty P.C. Diminished primary and secondary influenza virus-specific CD8(+) T-cell responses in CD4-depleted Ig(-/-) mice. J. Virol. 2000;74:9762-9765.
Not in our library10.1128/jvi.74.20.9762-9765.2000
171.
Strutt T.M., McKinstry K.K., Dibble J.P., Winchell C., Kuang Y., Curtis J.D., Huston G., Dutton R.W., Swain S.L. Memory CD4+ T cells induce innate responses independently of pathogen. Nat. Med. 2010;16(551p following 564):558-564.
Not in our library10.1038/nm.2142
172.
Teijaro J.R., Turner D., Pham Q., Wherry E.J., Lefrancois L., Farber D.L. Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J. Immunol. 2011;187:5510-5514.
Not in our library10.4049/jimmunol.1102243
173.
Brown D.M., Dilzer A.M., Meents D.L., Swain S.L. CD4 T cell-mediated protection from lethal influenza: Perforin and antibody-mediated mechanisms give a one-two punch. J. Immunol. 2006;177:2888-2898.
Not in our library10.4049/jimmunol.177.5.2888
174.
Graham M.B., Braciale V.L., Braciale T.J. Influenza virus-specific CD4+ T helper type 2 T lymphocytes do not promote recovery from experimental virus infection. J. Exp. Med. 1994;180:1273-1282.
Not in our library10.1084/jem.180.4.1273
175.
Wilkinson T.M., Li C.K., Chui C.S., Huang A.K., Perkins M., Liebner J.C., Lambkin-Williams R., Gilbert A., Oxford J., Nicholas B., et al. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat. Med. 2012;18:274-280.
Not in our library10.1038/nm.2612
176.
McKinstry K.K., Strutt T.M., Swain S.L. Hallmarks of CD4 T cell immunity against influenza. J. Intern. Med. 2011;269:507-518.
Not in our library10.1111/j.1365-2796.2011.02367.x
177.
Nakanishi Y., Lu B., Gerard C., Iwasaki A. CD8(+) T lymphocyte mobilization to virus-infected tissue requires CD4(+) T-cell help. Nature. 2009;462:510-513.
Not in our library10.1038/nature08511
178.
Assarsson E., Bui H.H., Sidney J., Zhang Q., Glenn J., Oseroff C., Mbawuike I.N., Alexander J., Newman M.J., Grey H., et al. Immunomic analysis of the repertoire of T-cell specificities for influenza A virus in humans. J. Virol. 2008;82:12241-12251.
Not in our library10.1128/jvi.01563-08
179.
Bednarek M.A., Sauma S.Y., Gammon M.C., Porter G., Tamhankar S., Williamson A.R., Zweerink H.J. The minimum peptide epitope from the influenza virus matrix protein. Extra and intracellular loading of HLA-A2. J. Immunol. 1991;147:4047-4053.
Not in our library
180.
Boon A.C., de Mutsert G., Graus Y.M., Fouchier R.A., Sintnicolaas K., Osterhaus A.D., Rimmelzwaan G.F. The magnitude and specificity of influenza A virus-specific cytotoxic T-lymphocyte responses in humans is related to HLA-A and -B phenotype. J. Virol. 2002;76:582-590.
Not in our library10.1128/jvi.76.2.582-590.2002
181.
Gotch F., McMichael A., Smith G., Moss B. Identification of viral molecules recognized by influenza-specific human cytotoxic T lymphocytes. J. Exp. Med. 1987;165:408-416.
Not in our library10.1084/jem.165.2.408
182.
Jameson J., Cruz J., Ennis F.A. Human cytotoxic T-lymphocyte repertoire to influenza A viruses. J. Virol. 1998;72:8682-8689.
Not in our library10.1128/jvi.72.11.8682-8689.1998
183.
Kreijtz J.H., de Mutsert G., van Baalen C.A., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Cross-recognition of avian H5N1 influenza virus by human cytotoxic T-lymphocyte populations directed to human influenza A virus. J. Virol. 2008;82:5161-5166.
Not in our library10.1128/jvi.02694-07
184.
Lee L.Y., Ha do L.A., Simmons C., de Jong M.D., Chau N.V., Schumacher R., Peng Y.C., McMichael A.J., Farrar J.J., Smith G.L., et al. Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. J. Clin. Investig. 2008;118:3478-3490.
Not in our library10.1172/jci32460
185.
Andrade F. Non-cytotoxic antiviral activities of granzymes in the context of the immune antiviral state. Immunol. Rev. 2010;235:128-146.
Not in our library10.1111/j.0105-2896.2010.00909.x
186.
Moffat J.M., Gebhardt T., Doherty P.C., Turner S.J., Mintern J.D. Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection. Eur. J. Immunol. 2009;39:1203-1210.
Not in our library10.1002/eji.200839183
187.
Topham D.J., Tripp R.A., Doherty P.C. CD8+ T cells clear influenza virus by perforin or Fas-dependent processes. J. Immunol. 1997;159:5197-5200.
Not in our library
188.
La Gruta N.L., Turner S.J., Doherty P.C. Hierarchies in cytokine expression profiles for acute and resolving influenza virus-specific CD8+ T cell responses: Correlation of cytokine profile and TCR avidity. J. Immunol. 2004;172:5553-5560.
Not in our library10.4049/jimmunol.172.9.5553
189.
Metkar S.S., Menaa C., Pardo J., Wang B., Wallich R., Freudenberg M., Kim S., Raja S.M., Shi L., Simon M.M., et al. Human and mouse granzyme A induce a proinflammatory cytokine response. Immunity. 2008;29:720-733.
Not in our library10.1016/j.immuni.2008.08.014
190.
van Domselaar R., Bovenschen N. Cell death-independent functions of granzymes: Hit viruses where it hurts. Rev. Med. Virol. 2011;21:301-314.
Not in our library10.1002/rmv.697
191.
La Gruta N.L., Kedzierska K., Stambas J., Doherty P.C. A question of self-preservation: Immunopathology in influenza virus infection. Immunol. Cell Biol. 2007;85:85-92.
Not in our library10.1038/sj.icb.7100026
192.
Woodland D.L., Hogan R.J., Zhong W. Cellular immunity and memory to respiratory virus infections. Immunol. Res. 2001;24:53-67.
Not in our library10.1385/ir:24:1:53
193.
Kedl R.M., Mescher M.F. Qualitative differences between naive and memory T cells make a major contribution to the more rapid and efficient memory CD8+ T cell response. J. Immunol. 1998;161:674-683.
Not in our library
194.
Lalvani A., Brookes R., Hambleton S., Britton W.J., Hill A.V., McMichael A.J. Rapid effector function in CD8+ memory T cells. J. Exp. Med. 1997;186:859-865.
Not in our library10.1084/jem.186.6.859
195.
Zimmermann C., Prevost-Blondel A., Blaser C., Pircher H. Kinetics of the response of naive and memory CD8 T cells to antigen: Similarities and differences. Eur. J. Immunol. 1999;29:284-290.
Not in our library10.1002/(sici)1521-4141(199901)29:01<284::aid-immu284>3.0.co;2-c
196.
DiSpirito J.R., Shen H. Quick to remember, slow to forget: Rapid recall responses of memory CD8+ T cells. Cell Res. 2010;20:13-23.
Not in our library10.1038/cr.2009.140
197.
Chang J.T., Palanivel V.R., Kinjyo I., Schambach F., Intlekofer A.M., Banerjee A., Longworth S.A., Vinup K.E., Mrass P., Oliaro J., et al. Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science. 2007;315:1687-1691.
Not in our library10.1126/science.1139393
198.
Hikono H., Kohlmeier J.E., Takamura S., Wittmer S.T., Roberts A.D., Woodland D.L. Activation phenotype, rather than central- or effector-memory phenotype, predicts the recall efficacy of memory CD8+ T cell. J. Exp. Med. 2007;204:1625-1636.
Not in our library10.1084/jem.20070322
199.
Sallusto F., Lenig D., Forster R., Lipp M., Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401:708-712.
Not in our library10.1038/44385
200.
van Gisbergen K.P., Klarenbeek P.L., Kragten N.A., Unger P.P., Nieuwenhuis M.B., Wensveen F.M., ten Brinke A., Tak P.P., Eldering E., Nolte M.A., et al. The costimulatory molecule CD27 maintains clonally diverse CD8(+) T cell responses of low antigen affinity to protect against viral variants. Immunity. 2011;35:97-108.
Not in our library10.1016/j.immuni.2011.04.020
201.
Wherry E.J., Teichgraber V., Becker T.C., Masopust D., Kaech S.M., Antia R., von Andrian U.H., Ahmed R. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat. Immunol. 2003;4:225-234.
Not in our library10.1038/ni889
202.
Bender B.S., Croghan T., Zhang L., Small P.A. Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J. Exp. Med. 1992;175:1143-1145.
Not in our library10.1084/jem.175.4.1143
203.
Graham M.B., Braciale T.J. Resistance to and recovery from lethal influenza virus infection in B lymphocyte-deficient mice. J. Exp. Med. 1997;186:2063-2068.
Not in our library10.1084/jem.186.12.2063
204.
Hillaire M.L., van Trierum S.E., Kreijtz J.H., Bodewes R., Geelhoed-Mieras M.M., Nieuwkoop N.J., Fouchier R.A., Kuiken T., Osterhaus A.D., Rimmelzwaan G.F. Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells. J. Gen. Virol. 2011;92:2339-2349.
Not in our library10.1099/vir.0.033076-0
205.
Kreijtz J.H., Bodewes R., van Amerongen G., Kuiken T., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice. Vaccine. 2007;25:612-620.
Not in our library10.1016/j.vaccine.2006.08.036
206.
Kreijtz J.H., Bodewes R., van den Brand J.M., de Mutsert G., Baas C., van Amerongen G., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus. Vaccine. 2009;27:4983-4989.
Not in our library10.1016/j.vaccine.2009.05.079
207.
Taylor P.M., Askonas B.A. Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo. Immunology. 1986;58:417-420.
Not in our library
208.
Hillaire M.L., Osterhaus A.D., Rimmelzwaan G.F. Induction of virus-specific cytotoxic T lymphocytes as a basis for the development of broadly protective influenza vaccines. J. Biomed. Biotechnol. 2011;2011:939860.
Not in our library10.1155/2011/939860
209.
Grebe K.M., Yewdell J.W., Bennink J.R. Heterosubtypic immunity to influenza A virus: Where do we stand? Microb. Infect. 2008;10:1024-1029.
Not in our library10.1016/j.micinf.2008.07.002
210.
Sridhar S., Begom S., Bermingham A., Ziegler T., Roberts K.L., Barclay W.S., Openshaw P., Lalvani A. Predominance of heterosubtypic IFN-gamma-only-secreting effector memory T cells in pandemic H1N1 naive adults. Eur. J. Immunol. 2012.
Not in our library10.1002/eji.201242504
211.
McMichael A.J., Gotch F.M., Noble G.R., Beare P.A. Cytotoxic T-cell immunity to influenza. New Engl. J. Med. 1983;309:13-17.
Not in our library10.1056/nejm198307073090103
212.
Epstein S.L. Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: An experiment of nature. J. Infect. Dis. 2006;193:49-53.
Not in our library10.1086/498980
213.
Slepushkin A.N. The effect of a previous attack of A1 influenza on susceptibility to A2 virus during the 1957 outbreak. Bull. World Health Organ. 1959;20:297-301.
Not in our library
214.
Smallman-Raynor M., Cliff A.D. Avian influenza A (H5N1) age distribution in humans. Emerg. Infect. Dis. 2007;13:510-512.
Not in our library10.3201/eid1303.060849
215.
Campbell D.J., Koch M.A. Phenotypical and functional specialization of FOXP3+ regulatory T cells. Nat. Rev. 2011;11:119-130.
Not in our library10.1038/nri2916
216.
Surls J., Nazarov-Stoica C., Kehl M., Casares S., Brumeanu T.D. Differential effect of CD4+Foxp3+ T-regulatory cells on the B and T helper cell responses to influenza virus vaccination. Vaccine. 2010;28:7319-7330.
Not in our library10.1016/j.vaccine.2010.08.074
217.
Kudva A., Scheller E.V., Robinson K.M., Crowe C.R., Choi S.M., Slight S.R., Khader S.A., Dubin P.J., Enelow R.I., Kolls J.K., et al. Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice. J. Immunol. 2011;186:1666-1674.
Not in our library10.4049/jimmunol.1002194
218.
Garcia-Sastre A., Egorov A., Matassov D., Brandt S., Levy D.E., Durbin J.E., Palese P., Muster T. Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology. 1998;252:324-330.
Not in our library10.1006/viro.1998.9508
219.
Influenza A and B viruses expressing altered NS1 proteins: A vaccine approach · 2000
Not checked
220.
Falcon A.M., Fernandez-Sesma A., Nakaya Y., Moran T.M., Ortin J., Garcia-Sastre A. Attenuation and immunogenicity in mice of temperature-sensitive influenza viruses expressing truncated NS1 proteins. J. Gen. Virol. 2005;86:2817-2821.
Not in our library10.1099/vir.0.80991-0
221.
Donelan N.R., Basler C.F., Garcia-Sastre A. A recombinant influenza A virus expressing an RNA-binding-defective NS1 protein induces high levels of beta interferon and is attenuated in mice. J. Virol. 2003;77:13257-13266.
Not in our library10.1128/jvi.77.24.13257-13266.2003
222.
Solorzano A., Webby R.J., Lager K.M., Janke B.H., Garcia-Sastre A., Richt J.A. Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs. J. Virol. 2005;79:7535-7543.
Not in our library10.1128/jvi.79.12.7535-7543.2005
223.
Richt J.A., Garcia-Sastre A. Attenuated influenza virus vaccines with modified NS1 proteins. Curr. Top. Microbiol. Immunol. 2009;333:177-195.
Not in our library10.1007/978-3-540-92165-3_9
224.
Sublingual immunization with a live attenuated influenza a virus lacking the nonstructural protein 1 induces broad protective immunity in mice. · 2012
Not checked
225.
Gack M.U., Albrecht R.A., Urano T., Inn K.S., Huang I.C., Carnero E., Farzan M., Inoue S., Jung J.U., Garcia-Sastre A. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe. 2009;5:439-449.
Not in our library10.1016/j.chom.2009.04.006
226.
Ludwig S., Wang X., Ehrhardt C., Zheng H., Donelan N., Planz O., Pleschka S., Garcia-Sastre A., Heins G., Wolff T. The influenza A virus NS1 protein inhibits activation of Jun N-terminal kinase and AP-1 transcription factors. J. Virol. 2002;76:11166-11171.
Not in our library10.1128/jvi.76.21.11166-11171.2002
227.
Talon J., Horvath C.M., Polley R., Basler C.F., Muster T., Palese P., Garcia-Sastre A. Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein. J. Virol. 2000;74:7989-7996.
Not in our library10.1128/jvi.74.17.7989-7996.2000
228.
Wang X., Li M., Zheng H., Muster T., Palese P., Beg A.A., Garcia-Sastre A. Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon. J. Virol. 2000;74:11566-11573.
Not in our library10.1128/jvi.74.24.11566-11573.2000
229.
Ruckle A., Haasbach E., Julkunen I., Planz O., Ehrhardt C., Ludwig S. The NS1 protein of influenza A virus blocks RIG-I mediated activation of the noncanonical NF-kappaB pathway and p52/RelB dependent gene expression in lung epithelial cells. J. Virol. 2012;86:10211-7.
Not in our library10.1128/jvi.00323-12
230.
Mibayashi M., Martinez-Sobrido L., Loo Y.M., Cardenas W.B., Gale M., Garcia-Sastre A. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J. Virol. 2007;81:514-524.
Not in our library10.1128/jvi.01265-06
231.
Opitz B., Rejaibi A., Dauber B., Eckhard J., Vinzing M., Schmeck B., Hippenstiel S., Suttorp N., Wolff T. IFNbeta induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein. Cell. Microbiol. 2007;9:930-938.
Not in our library10.1111/j.1462-5822.2006.00841.x
232.
Nemeroff M.E., Barabino S.M., Li Y., Keller W., Krug R.M. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol. Cell. 1998;1:991-1000.
Not in our library10.1016/s1097-2765(00)80099-4
233.
Noah D.L., Twu K.Y., Krug R.M. Cellular antiviral responses against influenza A virus are countered at the posttranscriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3' end processing of cellular pre-mRNAS. Virology. 2003;307:386-395.
Not in our library10.1016/s0042-6822(02)00127-7
234.
Das K., Ma L.C., Xiao R., Radvansky B., Aramini J., Zhao L., Marklund J., Kuo R.L., Twu K.Y., Arnold E., et al. Structural basis for suppression of a host antiviral response by influenza A virus. Proc. Natl. Acad. Sci. U. S. A. 2008;105:13093-13098.
Not in our library10.1073/pnas.0805213105
235.
Qian X.Y., Alonso-Caplen F., Krug R.M. Two functional domains of the influenza virus NS1 protein are required for regulation of nuclear export of mRNA. J. Virol. 1994;68:2433-2441.
Not in our library10.1128/jvi.68.4.2433-2441.1994
236.
Satterly N., Tsai P.L., van Deursen J., Nussenzveig D.R., Wang Y., Faria P.A., Levay A., Levy D.E., Fontoura B.M. Influenza virus targets the mRNA export machinery and the nuclear pore complex. Proc. Natl. Acad. Sci. U. S. A. 2007;104:1853-1858.
Not in our library10.1073/pnas.0610977104
237.
The Influenza Virus Protein PB1-F2 Inhibits the Induction of Type I Interferon at the Level of the MAVS Adaptor Protein · 2011
No notice
238.
Conenello G.M., Tisoncik J.R., Rosenzweig E., Varga Z.T., Palese P., Katze M.G. A single N66S mutation in the PB1-F2 protein of influenza A virus increases virulence by inhibiting the early interferon response in vivo. J. Virol. 2011;85:652-662.
Not in our library10.1128/jvi.01987-10
239.
Dudek S.E., Wixler L., Nordhoff C., Nordmann A., Anhlan D., Wixler V., Ludwig S. The influenza virus PB1-F2 protein has interferon antagonistic activity. Biol. Chem. 2011;392:1135-1144.
Not in our library10.1515/bc.2011.174
240.
Graef K.M., Vreede F.T., Lau Y.F., McCall A.W., Carr S.M., Subbarao K., Fodor E. The PB2 subunit of the influenza virus RNA polymerase affects virulence by interacting with the mitochondrial antiviral signaling protein and inhibiting expression of beta interferon. J. Virol. 2010;84:8433-8445.
Not in our library10.1128/jvi.00879-10
241.
Iwai A., Shiozaki T., Kawai T., Akira S., Kawaoka Y., Takada A., Kida H., Miyazaki T. Influenza A virus polymerase inhibits type I interferon induction by binding to interferon beta promoter stimulator 1. J. Biol. Chem. 2010;285:32064-32074.
Not in our library10.1074/jbc.m110.112458
242.
Guilligay D., Tarendeau F., Resa-Infante P., Coloma R., Crepin T., Sehr P., Lewis J., Ruigrok R.W., Ortin J., Hart D.J., et al. The structural basis for cap binding by influenza virus polymerase subunit PB2. Nat. Struct. Mol. Biol. 2008;15:500-506.
Not in our library10.1038/nsmb.1421
243.
Sugiyama K., Obayashi E., Kawaguchi A., Suzuki Y., Tame J.R., Nagata K., Park S.Y. Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase. EMBO J. 2009;28:1803-1811.
Not in our library10.1038/emboj.2009.138
244.
Dias A., Bouvier D., Crepin T., McCarthy A.A., Hart D.J., Baudin F., Cusack S., Ruigrok R.W. The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature. 2009;458:914-918.
Not in our library10.1038/nature07745
245.
Plotch S.J., Bouloy M., Ulmanen I., Krug R.M. A unique cap(m7GpppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell. 1981;23:847-858.
Not in our library10.1016/0092-8674(81)90449-9
246.
Yuan P., Bartlam M., Lou Z., Chen S., Zhou J., He X., Lv Z., Ge R., Li X., Deng T., et al. Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site. Nature. 2009;458:909-913.
Not in our library10.1038/nature07720
247.
Goodman A.G., Smith J.A., Balachandran S., Perwitasari O., Proll S.C., Thomas M.J., Korth M.J., Barber G.N., Schiff L.A., Katze M.G. The cellular protein P58IPK regulates influenza virus mRNA translation and replication through a PKR-mediated mechanism. J. Virol. 2007;81:2221-2230.
Not in our library10.1128/jvi.02151-06
248.
The molecular chaperone hsp40 regulates the activity of P58IPK, the cellular inhibitor of PKR · 1997
Not checked
249.
Sharma K., Tripathi S., Ranjan P., Kumar P., Garten R., Deyde V., Katz J.M., Cox N.J., Lal R.B., Sambhara S., et al. Influenza A virus nucleoprotein exploits Hsp40 to inhibit PKR activation. PLoS One. 2011;6:e20215.
Not in our library10.1371/journal.pone.0020215
250.
Guan Z., Liu D., Mi S., Zhang J., Ye Q., Wang M., Gao G.F., Yan J. Interaction of Hsp40 with influenza virus M2 protein: Implications for PKR signaling pathway. Protein Cell. 2010;1:944-955.
Not in our library10.1007/s13238-010-0115-x
251.
Influenza A Virus Inhibits Type I IFN Signaling via NF-κB-Dependent Induction of SOCS-3 Expression · 2008
No notice
252.
Pothlichet J., Chignard M., Si-Tahar M. Cutting edge: Innate immune response triggered by influenza A virus is negatively regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway. J. Immunol. 2008;180:2034-2038.
Not in our library10.4049/jimmunol.180.4.2034
253.
Boliar S., Chambers T.M. A new strategy of immune evasion by influenza A virus: Inhibition of monocyte differentiation into dendritic cells. Vet. Immunol. Immunopathol. 2010;136:201-210.
Not in our library10.1016/j.vetimm.2010.03.004
254.
Fernandez-Sesma A., Marukian S., Ebersole B.J., Kaminski D., Park M.S., Yuen T., Sealfon S.C., Garcia-Sastre A., Moran T.M. Influenza virus evades innate and adaptive immunity via the NS1 protein. J. Virol. 2006;80:6295-6304.
Not in our library10.1128/jvi.02381-05
255.
Guo H., Kumar P., Malarkannan S. Evasion of natural killer cells by influenza virus. J. Leukoc. Biol. 2011;89:189-194.
Not in our library10.1189/jlb.0610319
256.
Owen R.E., Yamada E., Thompson C.I., Phillipson L.J., Thompson C., Taylor E., Zambon M., Osborn H.M., Barclay W.S., Borrow P. Alterations in receptor binding properties of recent human influenza H3N2 viruses are associated with reduced natural killer cell lysis of infected cells. J. Virol. 2007;81:11170-11178.
Not in our library10.1128/jvi.01217-07
257.
Mao H., Tu W., Liu Y., Qin G., Zheng J., Chan P.L., Lam K.T., Peiris J.S., Lau Y.L. Inhibition of human natural killer cell activity by influenza virions and hemagglutinin. J. Virol. 2010;84:4148-4157.
Not in our library10.1128/jvi.02340-09
258.
Mao H., Tu W., Qin G., Law H.K., Sia S.F., Chan P.L., Liu Y., Lam K.T., Zheng J., Peiris M., et al. Influenza virus directly infects human natural killer cells and induces cell apoptosis. J. Virol. 2009;83:9215-9222.
Not in our library10.1128/jvi.00805-09
259.
Rambaut A., Pybus O.G., Nelson M.I., Viboud C., Taubenberger J.K., Holmes E.C. The genomic and epidemiological dynamics of human influenza A virus. Nature. 2008;453:615-619.
Not in our library10.1038/nature06945
260.
McHardy A.C., Adams B. The role of genomics in tracking the evolution of influenza A virus. PLoS Pathog. 2009;5:e1000566.
Not in our library10.1371/journal.ppat.1000566
261.
Sorrell E.M., Schrauwen E.J., Linster M., De Graaf M., Herfst S., Fouchier R.A. Predicting 'airborne' influenza viruses: (Trans-) mission impossible? Curr. Opin. Virol. 2011;1:635-642.
Not in our library10.1016/j.coviro.2011.07.003
262.
Bodewes R., Nieuwkoop N.J., Verburgh R.J., Fouchier R.A., Osterhaus A., Rimmelzwaan G.F. The use of influenza A viruses expressing reporter genes to assess the frequency of double infections in vitro. J. Gen. Virol. 2012;93:1645-1648.
Not in our library10.1099/vir.0.042671-0
263.
Ito T., Couceiro J.N., Kelm S., Baum L.G., Krauss S., Castrucci M.R., Donatelli I., Kida H., Paulson J.C., Webster R.G., et al. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J. Virol. 1998;72:7367-7373.
Not in our library10.1128/jvi.72.9.7367-7373.1998
264.
Ma W., Lager K.M., Vincent A.L., Janke B.H., Gramer M.R., Richt J.A. The role of swine in the generation of novel influenza viruses. Zoonoses Public Health. 2009;56:326-337.
Not in our library10.1111/j.1863-2378.2008.01217.x
265.
Suzuki Y., Ito T., Suzuki T., Holland R.E., Chambers T.M., Kiso M., Ishida H., Kawaoka Y. Sialic acid species as a determinant of the host range of influenza A viruses. J. Virol. 2000;74:11825-11831.
Not in our library10.1128/jvi.74.24.11825-11831.2000
266.
Claas E.C., Kawaoka Y., de Jong J.C., Masurel N., Webster R.G. Infection of children with avian-human reassortant influenza virus from pigs in Europe. Virology. 1994;204:453-457.
Not in our library10.1006/viro.1994.1553
267.
Pensaert M., Ottis K., Vandeputte J., Kaplan M.M., Bachmann P.A. Evidence for the natural transmission of influenza A virus from wild ducts to swine and its potential importance for man. Bull. World Health Organ. 1981;59:75-78.
Not in our library
268.
Influenza Pandemics of the 20th Century · 2006
No notice
269.
Smith G.J., Bahl J., Vijaykrishna D., Zhang J., Poon L.L., Chen H., Webster R.G., Peiris J.S., Guan Y. Dating the emergence of pandemic influenza viruses. Proc. Natl. Acad. Sci. U. S. A. 2009;106:11709-11712.
Not in our library10.1073/pnas.0904991106
270.
Scholtissek C., Rohde W., Von Hoyningen V., Rott R. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology. 1978;87:13-20.
Not in our library10.1016/0042-6822(78)90153-8
271.
Smith G.J., Vijaykrishna D., Bahl J., Lycett S.J., Worobey M., Pybus O.G., Ma S.K., Cheung C.L., Raghwani J., Bhatt S., et al. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature. 2009;459:1122-1125.
Not in our library10.1038/nature08182
272.
Thontiravong A., Kitikoon P., Wannaratana S., Tantilertcharoen R., Tuanudom R., Pakpinyo S., Sasipreeyajan J., Oraveerakul K., Amonsin A. Quail as a potential mixing vessel for the generation of new reassortant influenza A viruses. Vet. Microbiol. 2012;(in press).
Not in our library10.1016/j.vetmic.2012.05.043
273.
Han T., Marasco W.A. Structural basis of influenza virus neutralization. Ann. New York Acad. Sci. 2011;1217:178-190.
Not in our library10.1111/j.1749-6632.2010.05829.x
274.
Kwong P.D., Doyle M.L., Casper D.J., Cicala C., Leavitt S.A., Majeed S., Steenbeke T.D., Venturi M., Chaiken I., Fung M., et al. HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. Nature. 2002;420:678-682.
Not in our library10.1038/nature01188
275.
Wyatt R., Kwong P.D., Desjardins E., Sweet R.W., Robinson J., Hendrickson W.A., Sodroski J.G. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature. 1998;393:705-711.
Not in our library10.1038/31514
276.
Horst D., Verweij M.C., Davison A.J., Ressing M.E., Wiertz E.J. Viral evasion of T cell immunity: Ancient mechanisms offering new applications. Curr. Opin. Immunol. 2011;23:96-103.
Not in our library10.1016/j.coi.2010.11.005
277.
Berkhoff E.G., de Wit E., Geelhoed-Mieras M.M., Boon A.C., Symons J., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Functional constraints of influenza A virus epitopes limit escape from cytotoxic T lymphocytes. J. Virol. 2005;79:11239-11246.
Not in our library10.1128/jvi.79.17.11239-11246.2005
278.
Del Val M., Schlicht H.J., Ruppert T., Reddehase M.J., Koszinowski U.H. Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein. Cell. 1991;66:1145-1153.
Not in our library10.1016/0092-8674(91)90037-y
279.
Eisenlohr L.C., Yewdell J.W., Bennink J.R. Flanking sequences influence the presentation of an endogenously synthesized peptide to cytotoxic T lymphocytes. J. Exp. Med. 1992;175:481-487.
Not in our library10.1084/jem.175.2.481
280.
Neisig A., Roelse J., Sijts A.J., Ossendorp F., Feltkamp M.C., Kast W.M., Melief C.J., Neefjes J.J. Major differences in transporter associated with antigen presentation (TAP)-dependent translocation of MHC class I-presentable peptides and the effect of flanking sequences. J. Immunol. 1995;154:1273-1279.
Not in our library
281.
Milicic A., Price D.A., Zimbwa P., Booth B.L., Brown H.L., Easterbrook P.J., Olsen K., Robinson N., Gileadi U., Sewell A.K., et al. CD8+ T cell epitope-flanking mutations disrupt proteasomal processing of HIV-1 Nef. J. Immunol. 2005;175:4618-4626.
Not in our library10.4049/jimmunol.175.7.4618
282.
Berkhoff E.G., Boon A.C., Nieuwkoop N.J., Fouchier R.A., Sintnicolaas K., Osterhaus A.D., Rimmelzwaan G.F. A mutation in the HLA-B*2705-restricted NP383-391 epitope affects the human influenza A virus-specific cytotoxic T-lymphocyte response in vitro. J. Virol. 2004;78:5216-5222.
Not in our library10.1128/jvi.78.10.5216-5222.2004
283.
Berkhoff E.G., Geelhoed-Mieras M.M., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Assessment of the extent of variation in influenza A virus cytotoxic T-lymphocyte epitopes by using virus-specific CD8+ T-cell clones. J. Gen. Virol. 2007;88:530-535.
Not in our library10.1099/vir.0.82120-0
284.
Price G.E., Ou R., Jiang H., Huang L., Moskophidis D. Viral escape by selection of cytotoxic T cell-resistant variants in influenza A virus pneumonia. J. Exp. Med. 2000;191:1853-1867.
Not in our library10.1084/jem.191.11.1853
285.
Rimmelzwaan G.F., Boon A.C., Voeten J.T., Berkhoff E.G., Fouchier R.A., Osterhaus A.D. Sequence variation in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes. Virus Res. 2004;103:97-100.
Not in our library10.1016/j.virusres.2004.02.020
286.
Voeten J.T., Bestebroer T.M., Nieuwkoop N.J., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Antigenic drift in the influenza A virus (H3N2) nucleoprotein and escape from recognition by cytotoxic T lymphocytes. J. Virol. 2000;74:6800-6807.
Not in our library10.1128/jvi.74.15.6800-6807.2000
287.
Berkhoff E.G., Geelhoed-Mieras M.M., Verschuren E.J., van Baalen C.A., Gruters R.A., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. The loss of immunodominant epitopes affects interferon-gamma production and lytic activity of the human influenza virus-specific cytotoxic T lymphocyte response in vitro. Clin. Exp. Immunol. 2007;148:296-306.
Not in our library10.1111/j.1365-2249.2007.03340.x
288.
Boon A.C., de Mutsert G., Graus Y.M., Fouchier R.A., Sintnicolaas K., Osterhaus A.D., Rimmelzwaan G.F. Sequence variation in a newly identified HLA-B35-restricted epitope in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes. J. Virol. 2002;76:2567-2572.
Not in our library10.1128/jvi.76.5.2567-2572.2002
289.
Cale E.M., Bazick H.S., Rianprakaisang T.A., Alam S.M., Letvin N.L. Mutations in a dominant Nef epitope of simian immunodeficiency virus diminish TCR: Epitope peptide affinity but not epitope peptide:MHC class I binding. J. Immunol. 2011;187:3300-3313.
Not in our library10.4049/jimmunol.1101080
290.
Huet S., Nixon D.F., Rothbard J.B., Townsend A., Ellis S.A., McMichael A.J. Structural homologies between two HLA B27-restricted peptides suggest residues important for interaction with HLA B27. Int. Immunol. 1990;2:311-316.
Not in our library10.1093/intimm/2.4.311
291.
Gog J.R., Rimmelzwaan G.F., Osterhaus A.D., Grenfell B.T. Population dynamics of rapid fixation in cytotoxic T lymphocyte escape mutants of influenza A. Proc. Natl. Acad. Sci. U. S. A. 2003;100:11143-11147.
Not in our library10.1073/pnas.1830296100
292.
Boon A.C., de Mutsert G., van Baarle D., Smith D.J., Lapedes A.S., Fouchier R.A., Sintnicolaas K., Osterhaus A.D., Rimmelzwaan G.F. Recognition of homo- and heterosubtypic variants of influenza A viruses by human CD8+ T lymphocytes. J. Immunol. 2004;172:2453-2460.
Not in our library10.4049/jimmunol.172.4.2453
293.
Gras S., Kedzierski L., Valkenburg S.A., Laurie K., Liu Y.C., Denholm J.T., Richards M.J., Rimmelzwaan G.F., Kelso A., Doherty P.C., et al. Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses. Proc. Natl. Acad. Sci. U. S. A. 2010;107:12599-12604.
Not in our library10.1073/pnas.1007270107
294.
Berkhoff E.G., de Wit E., Geelhoed-Mieras M.M., Boon A.C., Symons J., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Fitness costs limit escape from cytotoxic T lymphocytes by influenza A viruses. Vaccine. 2006;24:6594-6596.
Not in our library10.1016/j.vaccine.2006.05.051
295.
Rimmelzwaan G.F., Berkhoff E.G., Nieuwkoop N.J., Fouchier R.A., Osterhaus A.D. Functional compensation of a detrimental amino acid substitution in a cytotoxic-T-lymphocyte epitope of influenza a viruses by comutations. J. Virol. 2004;78:8946-8949.
Not in our library10.1128/jvi.78.16.8946-8949.2004
296.
Rimmelzwaan G.F., Berkhoff E.G., Nieuwkoop N.J., Smith D.J., Fouchier R.A., Osterhaus A.D. Full restoration of viral fitness by multiple compensatory co-mutations in the nucleoprotein of influenza A virus cytotoxic T-lymphocyte escape mutants. J. Gen. Virol. 2005;86:1801-1805.
Not in our library10.1099/vir.0.80867-0
297.
Berkhoff E.G., Geelhoed-Mieras M.M., Jonges M., Smith D.J., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. An amino acid substitution in the influenza A virus hemagglutinin associated with escape from recognition by human virus-specific CD4+ T-cells. Virus Res. 2007;126:282-287.
Not in our library10.1016/j.virusres.2007.02.018
298.
Cox R.J., Brokstad K.A., Ogra P. Influenza virus: Immunity and vaccination strategies. Comparison of the immune response to inactivated and live, attenuated influenza vaccines. Scand. J. Immunol. 2004;59:1-15.
Not in our library10.1111/j.0300-9475.2004.01382.x
299.
Cell-mediated Protection in Influenza Infection · 2006
No notice
300.
Kreijtz J.H., Osterhaus A.D., Rimmelzwaan G.F. Vaccination strategies and vaccine formulations for epidemic and pandemic influenza control. Hum. Vaccine. 2009;5:126-135.
Not in our library10.4161/hv.5.3.6986
301.
Russell C.A., Jones T.C., Barr I.G., Cox N.J., Garten R.J., Gregory V., Gust I.D., Hampson A.W., Hay A.J., Hurt A.C., et al. Influenza vaccine strain selection and recent studies on the global migration of seasonal influenza viruses. Vaccine. 2008;26:D31-D34.
Not in our library10.1016/j.vaccine.2008.07.078
302.
de Jong J.C., Beyer W.E., Palache A.M., Rimmelzwaan G.F., Osterhaus A.D. Mismatch between the 1997/1998 influenza vaccine and the major epidemic A(H3N2) virus strain as the cause of an inadequate vaccine-induced antibody response to this strain in the elderly. J. Med. Virol. 2000;61:94-99.
Not in our library10.1002/(sici)1096-9071(200005)61:1<94::aid-jmv15>3.0.co;2-c
303.
Salzberg S. The contents of the syringe. Nature. 2008;454:160-161.
Not in our library10.1038/454160a
304.
Jin H., Zhou H., Liu H., Chan W., Adhikary L., Mahmood K., Lee M.S., Kemble G. Two residues in the hemagglutinin of A/Fujian/411/02-like influenza viruses are responsible for antigenic drift from A/Panama/2007/99. Virology. 2005;336:113-119.
Not in our library10.1016/j.virol.2005.03.010
305.
Evolution of H5N1 Avian Influenza Viruses in Asia · 2005
No notice
306.
Pada S., Tambyah P.A. Overview/reflections on the 2009 H1N1 pandemic. Microb. Infect. 2011;13:470-478.
Not in our library10.1016/j.micinf.2011.01.009
307.
Rockman S., Brown L. Pre-pandemic and pandemic influenza vaccines. Hum. Vaccine. 2010;6:792-801.
Not in our library10.4161/hv.6.10.12915
308.
Belshe R.B., Nichol K.L., Black S.B., Shinefield H., Cordova J., Walker R., Hessel C., Cho I., Mendelman P.M. Safety, efficacy, and effectiveness of live, attenuated, cold-adapted influenza vaccine in an indicated population aged 5-49 years. Clin. Infect. Dis. 2004;39:920-927.
Not in our library10.1086/423001
309.
Mossad S.B. Demystifying FluMist, a new intranasal, live influenza vaccine. Cleve. Clin. J. Med. 2003;70:801-806.
Not in our library10.3949/ccjm.70.9.801
310.
Beyer W.E., Palache A.M., de Jong J.C., Osterhaus A.D. Cold-adapted live influenza vaccine versus inactivated vaccine: Systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis. Vaccine. 2002;20:1340-1353.
Not in our library10.1016/s0264-410x(01)00471-6
311.
Rudenko L., van den Bosch H., Kiseleva I., Mironov A., Naikhin A., Larionova N., Bushmenkov D. Live attenuated pandemic influenza vaccine: Clinical studies on A/17/California/2009/38 (H1N1) and licensing of the Russian-developed technology to WHO for pandemic influenza preparedness in developing countries. Vaccine. 2011;29:A40-A44.
Not in our library10.1016/j.vaccine.2011.04.122
312.
Hoft D.F., Babusis E., Worku S., Spencer C.T., Lottenbach K., Truscott S.M., Abate G., Sakala I.G., Edwards K.M., Creech C.B., et al. Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children. J. Infect. Dis. 2011;204:845-853.
Not in our library10.1093/infdis/jir436
313.
He Q., Martinez-Sobrido L., Eko F.O., Palese P., Garcia-Sastre A., Lyn D., Okenu D., Bandea C., Ananaba G.A., Black C.M., et al. Live-attenuated influenza viruses as delivery vectors for Chlamydia vaccines. Immunology. 2007;122:28-37.
Not in our library10.1111/j.1365-2567.2007.02608.x
314.
Pica N., Langlois R.A., Krammer F., Margine I., Palese P. NS1-truncated live attenuated virus vaccine provides robust protection to aged mice from viral challenge. J. Virol. 2012.
Not in our library10.1128/jvi.01131-12
315.
Bodewes R., Kreijtz J.H., Rimmelzwaan G.F. Yearly influenza vaccinations: A double-edged sword? Lancet Infect. Dis. 2009;9:784-788.
Not in our library10.1016/s1473-3099(09)70263-4
316.
Bodewes R., Fraaij P.L., Geelhoed-Mieras M.M., van Baalen C.A., Tiddens H.A., van Rossum A.M., van der Klis F.R., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Annual vaccination against influenza virus hampers development of virus-specific CD8(+) T cell immunity in children. J. Virol. 2011;85:11995-12000.
Not in our library10.1128/jvi.05213-11
317.
Bodewes R., Kreijtz J.H., Baas C., Geelhoed-Mieras M.M., de Mutsert G., van Amerongen G., van den Brand J.M., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Vaccination against human influenza A/H3N2 virus prevents the induction of heterosubtypic immunity against lethal infection with avian influenza A/H5N1 virus. PLoS One. 2009;4:e5538.
Not in our library10.1371/journal.pone.0005538
318.
Bodewes R., Kreijtz J.H., Geelhoed-Mieras M.M., van Amerongen G., Verburgh R.J., van Trierum S.E., Kuiken T., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Vaccination against seasonal influenza A/H3N2 virus reduces the induction of heterosubtypic immunity against influenza A/H5N1 virus infection in ferrets. J. Virol. 2011;85:2695-2702.
Not in our library10.1128/jvi.02371-10
319.
Bodewes R., Kreijtz J.H., Hillaire M.L., Geelhoed-Mieras M.M., Fouchier R.A., Osterhaus A.D., Rimmelzwaan G.F. Vaccination with whole inactivated virus vaccine affects the induction of heterosubtypic immunity against influenza virus A/H5N1 and immunodominance of virus-specific CD8+ T-cell responses in mice. J. Gen. Virol. 2010;91:1743-1753.
Not in our library10.1099/vir.0.020784-0
320.
Evolutionarily Conserved Protein Sequences of Influenza A Viruses, Avian and Human, as Vaccine Targets · 2007
No notice
321.
Rimmelzwaan G.F., Fouchier R.A., Osterhaus A.D. Influenza virus-specific cytotoxic T lymphocytes: A correlate of protection and a basis for vaccine development. Curr. Opin. Biotechnol. 2007;18:529-536.
Not in our library10.1016/j.copbio.2007.11.002
322.
Daemen T., de Mare A., Bungener L., de Jonge J., Huckriede A., Wilschut J. Virosomes for antigen and DNA delivery. Adv. Drug Deliv. Rev. 2005;57:451-463.
Not in our library10.1016/j.addr.2004.09.005
323.
Berthoud T.K., Hamill M., Lillie P.J., Hwenda L., Collins K.A., Ewer K.J., Milicic A., Poyntz H.C., Lambe T., Fletcher H.A., et al. Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1. Clin. Infect. Dis. 2011;52:1-7.
Not in our library10.1093/cid/ciq015
324.
Liniger M., Zuniga A., Naim H.Y. Use of viral vectors for the development of vaccines. Expet Rev. Vaccine. 2007;6:255-266.
Not in our library10.1586/14760584.6.2.255
325.
Ulmer J.B. Influenza DNA vaccines. Vaccine. 2002;20:S74-S76.
Not in our library10.1016/s0264-410x(02)00136-6
326.
Rimmelzwaan G.F., Nieuwkoop N., Brandenburg A., Sutter G., Beyer W.E., Maher D., Bates J., Osterhaus A.D. A randomized, double blind study in young healthy adults comparing cell mediated and humoral immune responses induced by influenza ISCOM vaccines and conventional vaccines. Vaccine. 2000;19:1180-1187.
Not in our library10.1016/s0264-410x(00)00310-8
327.
Sambhara S., Woods S., Arpino R., Kurichh A., Tamane A., Underdown B., Klein M., Lovgren Bengtsson K., Morein B., Burt D. Heterotypic protection against influenza by immunostimulating complexes is associated with the induction of cross-reactive cytotoxic T lymphocytes. J. Infect. Dis. 1998;177:1266-1274.
Not in our library10.1086/515285
328.
Lipatov A.S., Gitelman A.K., Smirnov Yu A. Prevention and treatment of lethal influenza A virus bronchopneumonia in mice by monoclonal antibody against haemagglutinin stem region. Acta Virol. 1997;41:337-340.
Not in our library
329.
Fan J., Liang X., Horton M.S., Perry H.C., Citron M.P., Heidecker G.J., Fu T.M., Joyce J., Przysiecki C.T., Keller P.M., et al. Preclinical study of influenza virus A M2 peptide conjugate vaccines in mice, ferrets, and rhesus monkeys. Vaccine. 2004;22:2993-3003.
Not in our library10.1016/j.vaccine.2004.02.021
330.
Song J.M., Wang B.Z., Park K.M., Van Rooijen N., Quan F.S., Kim M.C., Jin H.T., Pekosz A., Compans R.W., Kang S.M. Influenza virus-like particles containing M2 induce broadly cross protective immunity. PLoS One. 2011;6:e14538.
Not in our library10.1371/journal.pone.0014538

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