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Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

Marc Desforges, Alain Le Coupanec, Philippe Dubeau and 4 more

Viruses · 2019 · Review · CC BY

doi:10.3390/v12010014

Abstract

Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 16, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

The central nervous system (CNS), a marvel of intricate cellular and molecular interactions, maintains life and orchestrates homeostasis. Unfortunately, the CNS is not immune to alterations that lead to neurological disease, some resulting from acute, persistent or latent viral infections. Several viruses have the ability to invade the CNS, where they can infect resident cells, including the neurons. Although rare, viral infections of the CNS do occur. However, their incidence in clinical practice is difficult to evaluate precisely. For instance, in cases of viral encephalitis involving the most prevalent viruses known to reach the CNS (mainly herpesviruses, arboviruses and enteroviruses), an actual viral presence can only be detected in 3 to 30 cases out of 100,000 persons. Considering all types of viral infections, between 6000 and 20,000 cases of encephalitis that require hospitalization occur every year in the United States, representing about 6 cases per 100,000 infected persons every year. As the estimated charge for each case lies between $58,000 and $89,600, an evaluation of the total annual health cost is of half a billion dollars. Due to the cost associated with patient care and treatment, CNS viral infections cause considerably more morbidity and disabilities in low-income/resource-poor countries.

Very common worldwide, viral infections of the respiratory tract represent a major problem for human and animal health, imposing a tremendous economic burden. These respiratory infections induce the most common illnesses and are a leading cause of morbidity and mortality in humans worldwide, causing critical problems in public health, especially in children, the elderly and immune-compromised individuals. Viruses represent the most prevalent pathogens present in the respiratory tract. Indeed, it is estimated that about 200 different viruses (including influenza viruses, coronaviruses, rhinoviruses, adenoviruses, metapneumoviruses, such as human metapneumovirus A1, as well as orthopneumoviruses, such as the human respiratory syncytial virus) can infect the human airway. Infants and children, as well as the elderly represent more vulnerable populations, in which viruses cause 95% and 40% of all respiratory diseases, respectively. Among the various respiratory viruses, some are constantly circulating every year in the human populations worldwide, where they can be associated with a plethora of symptoms, from common colds to more severe problems requiring hospitalization. Moreover, in addition to the many “regular” viruses that circulate and infect millions of people every year, new respiratory viral agents emerge from time to time, causing viral epidemics or pandemics associated with more serious symptoms, such as neurologic disorders. These peculiar events usually take place when RNA viruses like influenza A, human coronaviruses, such as MERS-CoV and SARS-CoV, or henipaviruses, present in an animal reservoir, cross the species barrier as an opportunistic strategy to adapt to new environments and/or new hosts. These zoonoses may have disastrous consequences in humans, and the burden is even higher if they have neurological consequences.

2. Viruses as Plausible Etiologic Agents in Neurological Disorders

Epithelial cells that line the respiratory tract are the first cells that can be infected by respiratory viruses. Most of these infections are self-limited and the virus is cleared by immunity with minimal clinical consequences. On the other hand, in more vulnerable individuals, viruses can also reach the lower respiratory tract where they cause more severe illnesses, such as bronchitis, pneumonia, exacerbations of asthma, chronic obstructive pulmonary disease (COPD) and different types of severe respiratory distress syndromes. Besides all these respiratory issues, accumulating evidence from the clinical/medical world strongly suggest that, being opportunistic pathogens, these viruses are able to escape the immune response and cause more severe respiratory diseases or even spread to extra-respiratory organs, including the central nervous system where they could infect resident cells and potentially induce other types of pathologies.

Like all types of viral agents, respiratory viruses may enter the CNS through the hematogenous or neuronal retrograde route. In the first, the CNS is being invaded by a viral agent which utilizes the bloodstream and in the latter, a given virus infects neurons in the periphery and uses the axonal transport machinery to gain access to the CNS. In the hematogenous route, a virus will either infect endothelial cells of the blood-brain-barrier (BBB) or epithelial cells of the blood-cerebrospinal fluid barrier (BCSFB) in the choroid plexus (CP) located in the ventricles of the brain, or leukocytes that will serve as a vector for dissemination towards the CNS. Viruses such as HIV, HSV, HCMV, enteroviruses such as coxsackievirus B3, flaviviruses, chikungunya virus (CHIKV) and echovirus 30 have all been shown to disseminate towards the CNS through the hematogenous route. Respiratory viruses such as RSV, henipaviruses, influenza A and B and enterovirus D68 are also sometimes found in the blood and, being neuroinvasive, they may therefore use the hematogenous route to reach the CNS. As they invade the human host through the airway, the same respiratory viruses may use the olfactory nerve to get access to the brain through the olfactory bulb. On the other hand, these viruses may also use other peripheral nerves like the trigeminal nerve, which possesses nociceptive neuronal cells present in the nasal cavity, or alternatively, the sensory fibers of the vagus nerve, which stems from the brainstem and innervates different organs of the respiratory tract, including the larynx, the trachea and the lungs.

Although the CNS seems difficult for viruses to penetrate, those pathogens that are able to do so may disseminate and replicate very actively and will possibly induce an overreacting innate immune response, which may be devastating. This situation may lead to severe meningitis and encephalitis that can be fatal, depending on several viral and host factors (including immunosuppression due to disease or medications) that may influence the severity of the disease.

Recently, a very interesting manuscript produced by Bookstaver and collaborators underlined the difficulties of precisely deciphering the epidemiology and identifying the causal agent of CNS infections. These difficulties are mainly due to the tremendous variation in the symptoms throughout the disease process and to the myriad of viruses that can cause CNS infections. As stated in their report, these authors underlined that the clinical portrait of viral infections is often nonspecific and requires the clinician to consider a range of differential diagnoses. Meningitis (infection/inflammation in meninges and the spinal cord) produces characteristic symptoms: fever, neck stiffness, photophobia and/or phonophobia. Encephalitis (infection/inflammation in the brain and surrounding tissues) may remain undiagnosed since the symptoms may be mild or non-existent. Symptoms may include altered brain function (altered mental status, personality change, abnormal behavior or speech), movement disorders and focal neurologic signs, such as hemiparesis, flaccid paralysis or paresthesia. Seizures can occur during both viral meningitis and encephalitis. Furthermore, viral encephalitis may also be difficult to distinguish from a non-viral encephalopathy or from an encephalopathy associated with a systemic viral infection occurring outside the CNS. Considering all these observations, it is therefore mandatory to insist on the importance of investigating the patient’s history before trying to identify a specific viral cause of a given neurological disorder.

In humans, a long list of viruses may invade the CNS, where they can infect the different resident cells (neuronal as well as glial cells) and possibly induce or contribute to neurological diseases, such as acute encephalitis, which can be from benign to fatal, depending on virus tropism, pathogenicity as well as other viral and patient characteristics. For instance, 30 years ago, the incidence of children encephalitis was as high as 16/100,000 in the second year of life, while progressively reducing to 1/100,000 by the age of 15. More recent data indicate that, in the USA, the herpes simplex virus (HSV) accounts for 50–75% of identified viral encephalitis cases, whereas the varicella zoster virus (VZV), enteroviruses and arboviruses are responsible for the majority of the other cases in the general population. Several other viruses can induce short-term neurological problems. For example, the rabies virus, herpes simplex and other herpes viruses (HHV), arthropod-borne flaviviruses such as the West Nile virus (WNV), Japanese encephalitis virus (JEV), chikungunya virus (CHIKV), Zika virus (ZIKV), alphaviruses such as the Venezuelan, Western and Eastern equine encephalitis viruses and enteroviruses affect millions of individuals worldwide and are sometimes associated with encephalitis, meningitis and other neurological disorders. The presence of viruses in the CNS may also result in long-term neurological diseases and/or sequelae. Human immunodeficiency virus (HIV) induces neurodegeneration, which lead to motor dysfunctions and cognitive impairments. Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease associated with reactivation of latent polyoma JC virus (JCV). Progressive tropical spastic paraparesis/HTLV-1-associated myelopathy (PTSP/HAM) is caused by human T-lymphotropic virus (HTLV-1) in 1–2% of infected individuals. Measles virus (MV), a highly contagious common virus, is associated with febrile illness, fever, cough and congestion, as well as a characteristic rash and Koplik’s spots. In rare circumstances, significant long-term CNS diseases, such as post-infectious encephalomyelitis (PIE) or acute disseminated encephalomyelitis (ADEM), occur in children and adolescents. Other examples of rare but devastating neurological disorders are measles inclusion body encephalitis (MIBE), mostly observed in immune-compromised patients, and subacute sclerosing panencephalitis (SSPE) that appears 6–10 years after infection.

Yet, with the exception of HIV, no specific virus has been constantly associated with specific human neurodegenerative disease. On the other hand, different human herpes viruses have been associated with Alzheimer’s disease (AD), multiple sclerosis (MS) and other types of long-term CNS disorders. As accurately stated by Majde, long-term neurodegenerative disorders may represent a “hit-and-run” type of pathology, since some symptoms are triggered by innate immunity associated with glial cell activation. Different forms of long-term sequelae (cognitive deficits and behavior changes, decreased memory/learning, hearing loss, neuromuscular outcomes/muscular weakness) were also observed following arboviral infections.

Including the few examples listed above, more than one hundred infectious agents (much of them being viruses) have been described as potentially encephalitogenic and an increasing number of positive viral identifications are now made with the help of modern molecular diagnostic methods. However, even after almost two decades into the 21st century and despite tremendous advances in clinical microbiology, the precise cause of CNS viral infections often remains unknown. Indeed, even though very important technical improvements were made in the capacity to detect the etiological agent, identification is still not possible in at least half of the cases. Among all the reported cases of encephalitis and other encephalopathies and even neurodegenerative processes, respiratory viruses could represent an underestimated part of etiological agents.

3. Respiratory Viruses with Neuroinvasive and Neurotropic Properties: Possible Associated Neuropathologies

Respiratory syncytial virus (RSV), a member of the Orthopneumovirus genus, infects approximately 70% of infants before the age of 1 and almost 100% by the age of 2 years old, making it the most common pathogen to cause lower respiratory tract infection such as bronchiolitis and pneumonia in infants worldwide. Recent evidence also indicates that severe respiratory diseases related to RSV are also frequent in immunocompromised adult patients and that the virus can also present neuroinvasive properties. Over the last five decades, a number of clinical cases have potentially associated the virus with CNS pathologies. RSV has been detected in the cerebrospinal fluid (CSF) of patients (mainly infants) and was associated with convulsions, febrile seizures and different types of encephalopathy, including clinical signs of ataxia and hormonal problems. Furthermore, RSV is now known to be able to infect sensory neurons in the lungs and to spread from the airways to the CNS in mice after intranasal inoculation, and to induce long-term sequelae such as behavioral and cognitive impairments.

An additional highly prevalent human respiratory pathogen with neuroinvasive and neurovirulent potential is the human metapneumovirus (hMPV). Discovered at the beginning of the 21st century in the Netherlands, it mainly causes respiratory diseases in newborns, infants and immunocompromised individuals. During the last two decades, sporadic cases of febrile seizures, encephalitis and encephalopathies (associated with epileptic symptoms) have been described. Viral material was detected within the CNS in some clinical cases of encephalitis/encephalopathy but, at present, no experimental data from any animal model exist that would help to understand the underlying mechanism associated with hMPV neuroinvasion and potential neurovirulence.

Hendra virus (HeV) and Nipah virus (NiV) are both highly pathogenic zoonotic members of the Henipavirus genus and represent important emerging viruses discovered in the late 1990s in Australia and southern Asia. They are the etiological agents of acute and severe respiratory disease in humans, including pneumonia, pulmonary edema and necrotizing alveolitis with hemorrhage. Although very similar at the genomic level, both viruses infect different intermediate animal reservoirs: the horse for HeV and the pig for NiV as a first step before crossing the barrier species towards humans. In humans, it can lead to different types of encephalitis, as several types of CNS resident cells (including neurons) can be infected. The neurological signs can include confusion, motor deficits, seizures, febrile encephalitic syndrome and a reduced level of consciousness. Even neuropsychiatric sequelae have been reported but it remains unclear whether a post-infectious encephalo-myelitis occurs following infection. The use of animal models showed that the main route of entry into the CNS is the olfactory nerve and that the Nipah virus may persist in different regions of the brain of grivets/green monkeys, reminiscent of relapsing and late-onset encephalitis observed in humans.

Influenza viruses are classified in four types: A, B, C and D. All are endemic viruses with types A and B being the most prevalent and causing the flu syndrome, characterized by chills, fever, headache, sore throat and muscle pain. They are responsible for seasonal epidemics that affect 3 to 5 million humans, among which 500,000 to 1 million cases are lethal each year. Associated with all major pandemics since the beginning of the 20th century, circulating influenza A presents the greatest threat to human health. Most influenza virus infections remain confined to the upper respiratory tract, although some can lead to severe cases and may result in pneumonia, acute respiratory distress syndrome (ARDS) and complications involving the CNS. Several studies have shown that influenza A can be associated with encephalitis, Reye’s syndrome, febrile seizure, Guillain–Barré syndrome, acute necrotizing encephalopathy and possibly acute disseminated encephalomyelitis (ADEM). Animal models have shown that, using either the olfactory route or vagus nerve, influenza A virus may have access to the CNS and alter the hippocampus and the regulation of neurotransmission, while affecting cognition and behavior as long-term sequelae. The influenza A virus has also been associated with the risk of developing Parkinson’s disease (PD) and has recently been shown to exacerbate experimental autoimmune encephalomyelitis (EAE), which is reminiscent of the observation that multiple sclerosis (MS) relapses have been associated with viral infections (including influenza A) of the upper respiratory tract.

Another source of concern when considering human respiratory pathogens associated with potential neuroinvasion and neurovirulence is the Enterovirus genus, which comprises hundreds of different serotypes, including polioviruses (PV), coxsackieviruses (CV), echoviruses, human rhinoviruses (HRV) and enteroviruses (EV). This genus constitutes one of the most common cause of respiratory infections (going from common cold to more severe illnesses) and some members (PV, EV-A71 and -D68, and to a lesser extent HRV) can invade and infect the CNS, with detrimental consequences. Even though extremely rare, HRV-induced meningitis and cerebellitis have been described. Although EV infections are mostly asymptomatic, outbreaks of EV-A71 and D68 have also been reported in different parts of the world during the last decade. EV-A71 is an etiological agent of the hand–foot–mouth disease (HFMD) and has occasionally been associated with upper respiratory tract infections. EV-D68 causes different types of upper and lower respiratory tract infections, including severe respiratory syndromes. Both serotypes have been associated with neurological disorders like acute flaccid paralysis (AFP), myelitis (AFM), meningitis and encephalitis.

Last but not least, human coronaviruses (HCoV) are another group of respiratory viruses that can naturally reach the CNS in humans and could potentially be associated with neurological symptoms. These ubiquitous human pathogens are molecularly related in structure and mode of replication with neuroinvasive animal coronaviruses like PHEV (porcine hemagglutinating encephalitis virus), FCoV (feline coronavirus) and the MHV (mouse hepatitis virus) strains of MuCoV, which can all reach the CNS and induce different types of neuropathologies. MHV represents the best described coronavirus involved in short- and long-term neurological disorders (a model for demyelinating MS-like diseases). Taken together, all these data bring us to consider a plausible involvement of HCoV in neurological diseases.

4. Human Coronaviruses: Eclosions of Recognized Respiratory Pathogens

The first strains of HCoV were isolated in the mid-60s from patients presenting an upper respiratory tract disease. Before the Severe Acute Respiratory Syndrome (SARS) appeared in 2002 and was associated with SARS-CoV, only two groups of HCoV, namely HCoV-229E (previous group 1, now classified as Alphacoronavirus) and HCoV-OC43 (previous group 2, now classified as Betacoronavirus) were known. Several new coronaviruses have now been identified, including three that infect humans: alphacoronavirus HCoV-NL63 and betacoronaviruses HCoV-HKU1 and MERS-CoV.

The HCoV-229E, -OC43, -NL63 and -HKU1 strains are endemic worldwide and exist in different genotypes. In immunocompetent individuals they usually infect the upper respiratory tract, where they are mainly associated with 15–30% of upper respiratory tract infections (URI): rhinitis, laryngitis/pharyngitis as well as otitis. Being highly opportunistic pathogens, HCoV can reach the lower respiratory tract and be associated with more severe illnesses, such as bronchitis, bronchiolitis, pneumonia, exacerbations of asthma and respiratory distress syndrome.

The 2002–2003 SARS pandemic was caused by a coronavirus that emerged from bats (first reservoir) to infect palm civets (intermediary reservoir) and then humans. A total of 8096 probable cases were reported and almost 10% (774 cases in more than 30 countries) of these resulted in death. The clinical portrait was described as an initial flu-like syndrome, followed by a respiratory syndrome associated with cough and dyspnea, complicated with the “real” severe acute respiratory syndrome (SARS) in about 20% of the patients. In addition, multiple organ failure was observed in several SARS-CoV-infected patients.

In the fall of 2012, individuals travelling from the Arabian Peninsula to the United Kingdom were affected by the Middle-East Respiratory Syndrome (MERS), a severe lower respiratory tract infection that resembled SARS, leading also to gastrointestinal symptoms and renal failure among some patients. Molecular sequencing rapidly showed that the new epidemic was caused by a new coronavirus: the MERS-CoV. MERS-CoV most probably originated from bats before infecting an intermediary reservoir (the dromedary camel), and also represented a zoonotic transmission to humans. Phylogenetic analyses suggest that there have been multiple independent zoonotic introductions of the virus in the human population. Moreover, nosocomial transmission was observed in multiple hospitals in Saudi Arabia.

Although possible, human-to-human MERS-CoV transmission appears inefficient as it requires extended close contact with an infected individual. Consequently, most transmission have occurred among patients’ families and healthcare workers (clusters of transmission). A more efficient human-to-human transmission was observed in South Korea, during the 2015 outbreak of MERS-CoV. Even though it has propagated to a few thousand people and possesses a high degree of virulence, MERS-CoV seems mostly restricted to the Arabic peninsula and is not currently considered an important pandemic threat. However, virus surveillance and better characterization are warranted, in order to be prompt to respond to any change in that matter.

As of October 8, 2019, the World Health Organization (WHO) reported that MERS-CoV had spread to at least 27 different countries, where 2468 laboratory-confirmed human cases have been identified with 851 being fatal (https://www.who.int/emergencies/mers-cov/en/). As observed for the four circulating strains of HCoV, both SARS-CoV and MERS-CoV usually induce more severe illnesses, and strike stronger in vulnerable populations such as the elderly, infants, immune-compromised individuals or patients with comorbidities.

4.1. Human Coronaviruses: Pathogens Causing Illnesses Outside the Respiratory Tract

Over the years, like SARS- and MERS-CoV, the four endemic HCoV have also been identified as possible etiological agents for pathologies outside the respiratory tract. Indeed, myocarditis, meningitis, severe diarrhea (and other gastrointestinal problems) and multi-organ failure have been reported, especially in children. Recent investigations on HCoV as enteric pathogens demonstrated that all HCoV strains can be found in stool samples of children with acute gastroenteritis; however, no evidence of association could yet be clearly demonstrated with disease etiology. Different reports also presented a possible link between the presence of HCoV within the human central nervous system (CNS) and some neurological disorders among patients examined. Like all viruses, HCoV may enter the CNS through the hematogenous or neuronal retrograde route.

4.1.1. Possible Mechanisms of HCoV Neuroinvasiveness

In the human airways, HCoV infection may lead to the disruption of the nasal epithelium and, although they bud and are released mostly on the apical side of the epithelial cells, a significant amount of viruses is also released from the basolateral side. Thus, although HCoV infections are, most of the time, restricted to the airways, they may under poorly understood conditions pass through the epithelium barrier and reach the bloodstream or lymph and propagate towards other tissues, including the CNS; this was also suggested for other respiratory viruses that can reach the human CNS, namely, RSV, Nipah virus and influenza virus.

Different strains of HCoV, including SARS-CoV, can infect different myeloid cells to manipulate the innate immunity and to disseminate to other tissues, including the CNS, where they may be associated with other type of pathologies, especially in immunocompromised individuals as it was observed for murine cytomegalovirus (MCMV). Moreover, persistently-infected leukocytes may serve as a reservoir and vector for neuroinvasive HCoV. Therefore, neuroinvasive HCoV could use the hematogenous route to penetrate into the CNS.

The second form of any viral spread towards the CNS is through neuronal dissemination, where a given virus infects neurons in the periphery and uses the machinery of active transport within those cells in order to gain access to the CNS. Although the olfactory bulb is highly efficient at controlling neuroinvasion, several viruses have been shown to enter CNS through the olfactory route. After an intranasal infection, both HCoV-OC43 and SARS-CoV were shown to infect the respiratory tract in mice and to be neuroinvasive. Over the years, we and others have gathered data showing that HCoV-OC43 is naturally neuroinvasive in both mice and humans. Experimental intranasal infections of susceptible mice also indicate that, once it has invaded the CNS, the virus disseminated to several regions of the brain and the brainstem before it eventually reaches the spinal cord. Furthermore, based on more recent work, Figure 1 illustrates the olfactory route, which is clearly the main route of neuroinvasion used by HCoV-OC43, as well as the early steps of subsequent neuropropagation within the CNS in susceptible mice and recapitulates the suggested equivalent pathway in humans. Nevertheless, our data suggest that HCoV-OC43 may also invade the CNS from the external environment through other pathways involving other cranial peripheral nerves, reminiscent of what was shown for other human respiratory viruses such as RSV and influenza virus. Therefore, on the one hand, an apparently innocuous human respiratory pathogen such as the HCoV may reach the CNS by different routes and induce short-term illnesses, such as encephalitis. On the other hand, it may persist in resident cells of the human CNS and may become a factor or co-factor of neuropathogenesis associated with long-term neurological sequelae in genetically or otherwise predisposed individuals.

4.1.2. Human Coronaviruses in the CNS: Possible Associated Neurological Pathologies

Because of their natural neuroinvasive potential in humans and animals, a possible association between the presence of ubiquitous human coronaviruses in the triggering or exacerbation of neurological human pathologies has often been suggested over the years. It is now accepted that HCoV are not always confined to the upper respiratory tract and that they can invade the CNS. As other viruses listed herein, HCoV are neurotropic and potentially neurovirulent. Even though no clear cause and effect link has ever been made with the onset of human neurological diseases, their neuropathogenicity is being increasingly recognized in humans, as several recent reports associated cases of encephalitis, acute flaccid paralysis and other neurological symptoms, including possible complications of HCoV infection such as Guillain–Barré syndrome or ADEM. The presence and persistence of HCoV in human brains was proposed to cause long-term sequelae related to the development or aggravation of chronic neurological diseases. Given their high prevalence, long-term persistence and newly recognized neuropathogenesis, HCoV disease burden could currently be underestimated. This suggest that better surveillance, diagnoses and deepened virus–host interactions studies are warranted in order to gather more knowledge that will make possible the development of therapeutic strategies to prevent or treat occurrences.

Potential Short-Term Neuropathologies

SARS-CoV, HCoV-OC43 and -229E are naturally neuroinvasive and neurotropic in humans and therefore potentially neurovirulent. Furthermore, animal models showed that SARS-CoV could invade the CNS primarily through the olfactory route or even after an intra-peritoneal infection, and induce neuronal cell death. To our knowledge, no reports on the presence of the three other coronaviruses that infect humans in the CNS have been published. However, neurological symptoms have been described in patients infected by all three viruses.

Making use of our in vivo model of HCoV neuropathogenesis, relying on the natural susceptibility of mice to HCoV-OC43—the most prevalent strain among endemic HCoV—encephalitis and transient flaccid paralysis associated with propagation towards the spinal cord and demyelination and long-term persistence in surviving mice were observed; thus, recapitulating the neurological afflictions reported in some patients infected by HCoV. Although we must interpret data obtained in rodents with all the caution dictated by the use of a non-human host, it is likely that the underlying mechanisms described will have relevance to the human situation or at least provide leads to investigate neurotropic HCoV in humans.

In susceptible mice, HCoV-OC43 has a selective tropism for neurons in which it is able to use axonal transport as a way of neuron-to-neuron propagation. These results, together with data harvested with the use of microfluidic devices (Xona microfluidic), helped to elaborate a putative model of propagation adapted from Tomishima and Enquist, in which infectious HCoV-OC43 could either be assembled in the cell body or at different points along the axon using the anterograde axonal transport to propagate between neurons or from neurons to glial cells surrounding neurons in the CNS (Figure 2). Furthermore, based on previous data using different mutant recombinant viruses harboring mutation in the S protein and making use of a luciferase expressing recombinant HCoV-OC43, we are now showing that the rate and success of virus propagation towards the spinal cord, in part through the neuron-to-neuron pathway, correlates with the exacerbation of neurovirulence (Figure 3).

HCoV-OC43 structural and accessory proteins are important for infection and some clearly represent virulence factors. Using neuronal cell cultures and our murine model, we gathered data indicating that some of these proteins also play a significant role in viral dissemination and now aim to exploit these promising leads to fully understand the course and determinants of propagation to and through the CNS and complete the neurologic portrait of short term HCoV neuropathogenesis.

Potential Long-Term Neuropathologies and Sequelae

The presence of HCoV RNA in the human CNS establishes the natural neuroinvasive properties of these respiratory viral agents. Moreover, it also suggests that they persist in human CNS as they do in human neural cells and in the CNS of mice that survive acute encephalitis. These surviving mice exhibited long-term sequelae associated with decreased activity in an open field test and a reduced hippocampus with neuronal loss in the CA1 and CA3 layers, reminiscent of what was observed after infection by the influenza A virus and RSV and to the significant loss of synapses within the CA3 region after infection by WNV.

The precise and complete etiology of several long-term neurological pathologies still represent a conundrum. Multiple sclerosis (MS) represents one such neurological disease for which an infectious agent or agents may play a triggering role, with viruses the most likely culprit in genetically predisposed individuals. It has been suggested that several neurotropic viruses could be involved in MS pathogenesis but that they may do so through similar direct and/or indirect mechanisms. However, although research has not yet led to a direct link to any specific virus, association of coronaviruses with MS has been suggested. Even though HCoV-OC43 and -229E were detected in some control brains and in some brains coming from patients with different neurological diseases, there was a significantly higher prevalence of HCoV-OC43 in brains of MS patients. Moreover, autoreactive T cells were able to recognize both viral and myelin antigens in MS patients but not in controls during infection by HCoV-OC43 and HCoV-229E. Thus, the immune response may participate in the induction or exacerbation of long-term neuropathologies such as MS in genetically or otherwise susceptible individuals. Furthermore, it was shown that in recombination activation gene (RAG) knock-out mice, HCoV-OC43-induced encephalitis could be partially mediated by the T-cell response to infection. This underlines the possibility that, like its murine counterpart MHV, long term infection of the CNS by HCoV may participate in the induction of demyelinating MS-like lesions.

4.1.3. Mechanisms of HCoV-Induced Neurodegeneration: Possible Associated Neuropathologies

Immune cell infiltration and cytokine production were observed in the mouse CNS after infection by HCoV-OC43. This immune response was significantly increased after infection by viral variants, which harbor mutations in the viral glycoprotein (S). These variants also induced glutamate excitotoxicity, thus increasing damage to neurons and/or disturbing glutamate homeostasis and thereby contributing to neuronal degeneration and hind-limb paralysis and possible demyelination. The degeneration of neurons may eventually lead to death of these essential cells by directly generating a cytotoxic insult related to viral replication and/or to the induction of different regulated cell death (RCD) pathways. Our results indicate that the underlying mechanisms appear to involve different cellular factors and pathways of RCD, described and reviewed elsewhere.

Virus–cell interactions are always important in the regulation of cell response to infection. For HCoV-OC43, we clearly showed that the viral S and E proteins are important factors of neurovirulence, neuropropagation and neurodegeneration of infected cells. We have also demonstrated that the HE protein is important for the production of infectious HCoV-OC43 and for efficient spreading between neuronal cells, suggesting an attenuation of the eventual spread into the CNS of viruses made deficient in fully active HE protein, potentially associated with a reduced neurovirulence. Coronavirus accessory proteins have been extensively studied and are now considered as important viral factors of virulence implicated in pathogenesis while counteracting innate immunity. Two of these accessory proteins (ns2 and ns5) produced during infection by HCoV-OC43 play a significant role in virulence and pathogenesis in the mouse CNS.

Like for several other respiratory viruses, accumulating evidence now indicate that HCoV are neuroinvasive in humans and we hypothesize that these recognized respiratory pathogens are potentially neurovirulent as well, as they could participate in short- and long-term neurological disorders either as a result of inadequate host immune responses and/or viral propagation in the CNS, which directly induces damage to resident cells. With that in mind, one can envisage that, under the right circumstances, HCoV may successfully reach and colonize the CNS, an issue largely deserted and possibly underestimated by the scientific community that has impacted or will impact the life of several unknowing individuals. In acute encephalitis, viral replication occurs in the brain tissue itself, possibly causing destructive lesions of the nervous tissue with different outcomes depending on the infected regions. As previously mentioned, HCoV may persist in the human CNS as it does in mice and potentially be associated with different types of long-term sequelae and chronic human neurological diseases.

5. Conclusions

In their famous review on CNS viral infection, published a few years ago, Koyuncu et al. insisted that, under the right conditions, all viruses can have access to the CNS. What “under the right conditions” means certainly represents a subject of debate among virologist and physicians. Nevertheless, as stated in the introduction of this review, viral factors (mutations in specific virulence genes), host factors (immunodepression, age) or a mixture of both (underlining the importance of virus–host interactions), are all good candidates to refer to if one intends to find the beginning of an explanation. A fast and accurate diagnosis would certainly improve prognosis for patients with a suspected CNS infection. Identification of a specific virus provides relevant information on how to treat a patient; therefore, the development of modern technologies, such as high throughput sequencing (Next Generation Sequencing) are warranted as it represents a potentially unbiased marvelous tool for rapid and robust diagnosis of unexplained encephalitis or other types of encephalopathies or neuronal manifestations, especially in the context where more traditional techniques have failed to identify the etiological agent. Therefore, although our attention is mainly on a few different viruses such as HSV, arboviruses and enteroviruses, it may now be the time to look at CNS viral infection from another perspective. These viruses truly represent an important proportion of CNS viral infection associated with encephalitis, meningitis, myelitis and long-term neurological disorders. Nevertheless, accumulating evidence in the scientific literature strongly suggest that many other viral candidates could be underestimated in that matter.

Several human respiratory viruses are neuroinvasive and neurotropic, with potential neuropathological consequences in vulnerable populations. Understanding the underpinning mechanisms of neuroinvasion and interaction of respiratory viruses (including HCoV) with the nervous system is essential to evaluate potentially pathological short- and long-term consequences. However, viral infections related to diseases that are rare manifestations of an infection (like long term chronic neurological diseases), represent situations where Koch’s postulates need to be modified. A series of new criteria, adapted from Sir Austin Bradford Hill, for causation was elaborated by Giovannoni and collaborators concerning the plausible viral hypothesis in MS. These criteria certainly represent a pertinent tool to evaluate the involvement of human respiratory viruses as a factor that could influence long-term human neurological diseases. To continue the gathering of epidemiological data is justified to evaluate the clear cause and effect link between neuroinvasive respiratory viruses and short- and long-term human neurological diseases. Understanding mechanisms of virus neuroinvasion and interactions with the central nervous system is essential for different reasons. First, to help better understand potentially pathologically relevant consequences of infection, and second in the design of novel diagnostic and intervention strategies that will help uncover potential “druggable” molecular virus–host interfaces highly relevant to symptoms of various neurological diseases with a viral involvement.

References 326

  1. 1.

    Bale J.F. Virus and Immune-Mediated Encephalitides: Epidemiology, Diagnosis, Treatment, and Prevention. Pediatr. Neurol. 2015;53:3-12.

    Not in our library10.1016/j.pediatrneurol.2015.03.013

  2. 2.

    Mailles A., Stahl J.P., Bloch K.C. Update and new insights in encephalitis. Clin. Microbiol. Infect. 2017;23:607-613.

    Not in our library10.1016/j.cmi.2017.05.002

  3. 3.

    Big C., Reineck L.A., Aronoff D.M. Viral infections of the central nervous system: A case-based review. Clin. Med. Res. 2009;7:142-146.

    Not in our library10.3121/cmr.2009.864

  4. 4.

    Tyler K.L. Acute Viral Encephalitis. N. Engl. J. Med. 2018;379:557-566.

    Not in our library10.1056/nejmra1708714

  5. 5.

    Griffin D.E. Emergence and re-emergence of viral diseases of the central nervous system. Prog. Neurobiol. 2010;91:95-101.

    Not in our library10.1016/j.pneurobio.2009.12.003

  6. 6.

    John C.C., Carabin H., Montano S.M., Bangirana P., Zunt J.R., Peterson P.K. Global research priorities for infections that affect the nervous system. Nature. 2015;527:S178-S186.

    Not in our library10.1038/nature16033

  7. 7.

    Vareille M., Kieninger E., Edwards M.R., Regamey N. The airway epithelium: Soldier in the fight against respiratory viruses. Clin. Microbiol. Rev. 2011;24:210-229.

    Not in our library10.1128/cmr.00014-10

  8. 8.
    Neurologic Alterations Due to Respiratory Virus Infections · 2018
    No notice
  9. 9.

    Cesario T.C. Viruses associated with pneumonia in adults. Clin. Infect. Dis. 2012;55:107-113.

    Not in our library10.1093/cid/cis297

  10. 10.

    Ison M.G., Hayden F.G. Viral infections in immunocompromised patients: What’s new with respiratory viruses? Curr. Opin. Infect. Dis. 2002;15:355-367.

    Not in our library10.1097/00001432-200208000-00002

  11. 11.

    Jartti T., Jartti L., Ruuskanen O., Soderlund-Venermo M. New respiratory viral infections. Curr. Opin. Pulm. Med. 2012;18:271-278.

    Not in our library10.1097/mcp.0b013e328351f8d4

  12. 12.

    Sloots T.P., Whiley D.M., Lambert S.B., Nissen M.D. Emerging respiratory agents: New viruses for old diseases? J. Clin. Virol. 2008;42:233-243.

    Not in our library10.1016/j.jcv.2008.03.002

  13. 13.

    Brouard J., Vabret A., Nimal-Cuvillon D., Bach N., Bessiere A., Arion A., Freymuth F. Epidemiology of acute upper and lower respiratory tract infections in children. Rev. Prat. 2007;57:1759-1766.

    Not in our library

  14. 14.

    Nicholls J.M., Butany J., Poon L.L., Chan K.H., Beh S.L., Poutanen S., Peiris J.S., Wong M. Time course and cellular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS. PLoS Med. 2006;3:e27.

    Not in our library10.1371/journal.pmed.0030027

  15. 15.

    Talbot H.K., Falsey A.R. The diagnosis of viral respiratory disease in older adults. Clin. Infect. Dis. 2010;50:747-751.

    Not in our library10.1086/650486

  16. 16.

    Tregoning J.S., Schwarze J. Respiratory viral infections in infants: Causes, clinical symptoms, virology, and immunology. Clin. Microbiol. Rev. 2010;23:74-98.

    Not in our library10.1128/cmr.00032-09

  17. 17.

    Pochon C., Voigt S. Respiratory Virus Infections in Hematopoietic Cell Transplant Recipients. Front. Microbiol. 2018;9:3294.

    Not in our library10.3389/fmicb.2018.03294

  18. 18.

    Coverstone A.M., Wang L., Sumino K. Beyond Respiratory Syncytial Virus and Rhinovirus in the Pathogenesis and Exacerbation of Asthma: The Role of Metapneumovirus, Bocavirus and Influenza Virus. Immunol. Allergy Clin. North. Am. 2019;39:391-401.

    Not in our library10.1016/j.iac.2019.03.007

  19. 19.

    Linden D., Guo-Parke H., Coyle P.V., Fairley D., McAuley D.F., Taggart C.C., Kidney J. Respiratory viral infection: A potential “missing link” in the pathogenesis of COPD. Eur. Respir. Rev. 2019;28.

    Not in our library10.1183/16000617.0063-2018

  20. 20.

    Nichols W.G., Peck Campbell A.J., Boeckh M. Respiratory viruses other than influenza virus: Impact and therapeutic advances. Clin. Microbiol. Rev. 2008;21:274-290.

    Not in our library10.1128/cmr.00045-07

  21. 21.

    Kustin T., Ling G., Sharabi S., Ram D., Friedman N., Zuckerman N., Bucris E.D., Glatman-Freedman A., Stern A., Mandelboim M. A method to identify respiratory virus infections in clinical samples using next-generation sequencing. Sci. Rep. 2019;9:2606.

    Not in our library10.1038/s41598-018-37483-w

  22. 22.

    Berry M., Gamieldien J., Fielding B.C. Identification of new respiratory viruses in the new millennium. Viruses. 2015;7:996-1019.

    Not in our library10.3390/v7030996

  23. 23.

    Paden C.R., Yusof M., Al Hammadi Z.M., Queen K., Tao Y., Eltahir Y.M., Elsayed E.A., Marzoug B.A., Bensalah O.K.A., Khalafalla A.I., et al. Zoonotic origin and transmission of Middle East respiratory syndrome coronavirus in the UAE. Zoonoses Public Health. 2018;65:322-333.

    Not in our library10.1111/zph.12435

  24. 24.

    Vonesch N., Binazzi A., Bonafede M., Melis P., Ruggieri A., Iavicoli S., Tomao P. Emerging zoonotic viral infections of occupational health importance. Pathog. Dis. 2019;77.

    Not in our library10.1093/femspd/ftz018

  25. 25.

    Li W., Shi Z., Yu M., Ren W., Smith C., Epstein J.H., Wang H., Crameri G., Hu Z., Zhang H., et al. Bats are natural reservoirs of SARS-like coronaviruses. Science. 2005;310:676-679.

    Not in our library10.1126/science.1118391

  26. 26.

    Corman V.M., Muth D., Niemeyer D., Drosten C. Hosts and Sources of Endemic Human Coronaviruses. Adv. Virus. Res. 2018;100:163-188.

    Not in our library10.1016/bs.aivir.2018.01.001

  27. 27.

    Sayed A., Bottu A., Qaisar M., Mane M.P., Acharya Y. Nipah virus: A narrative review of viral characteristics and epidemiological determinants. Public Health. 2019;173:97-104.

    Not in our library10.1016/j.puhe.2019.05.019

  28. 28.
    Animal influenza virus infections in humans: A commentary · 2019
    Not checked
  29. 29.

    Lyons J., McArthur J. Emerging infections of the central nervous system. Curr. Infect. Dis. Rep. 2013;15:576-582.

    Not in our library10.1007/s11908-013-0377-6

  30. 30.
    Influenza virus-related critical illness: pathophysiology and epidemiology · 2019
    No notice
  31. 31.

    Vabret A., Dina J., Brison E., Brouard J., Freymuth F. Human coronaviruses. Pathol. Biol. 2009;57:149-160.

    Not in our library10.1016/j.patbio.2008.02.018

  32. 32.

    Antonucci R., Chiappe S., Porcella A., Rosatelli D., Fanos V. Bronchiolitis-associated encephalopathy in critically-ill infants: An underestimated complication? J. Matern Fetal Neonatal Med. 2010;23:431-436.

    Not in our library10.3109/14767050903184181

  33. 33.

    Desforges M., Le Coupanec A., Brison E., Meessen-Pinard M., Talbot P.J. Neuroinvasive and neurotropic human respiratory coronaviruses: Potential neurovirulent agents in humans. Adv. Exp. Med. Biol. 2014;807:75-96.

    Not in our library10.1007/978-81-322-1777-0_6

  34. 34.

    McGavern D.B., Kang S.S. Illuminating viral infections in the nervous system. Nat. Rev. Immunol. 2011;11:318-329.

    Not in our library10.1038/nri2971

  35. 35.

    Koyuncu O.O., Hogue I.B., Enquist L.W. Virus infections in the nervous system. Cell Host Microbe. 2013;13:379-393.

    Not in our library10.1016/j.chom.2013.03.010

  36. 36.

    Berth S.H., Leopold P.L., Morfini G.N. Virus-induced neuronal dysfunction and degeneration. Front. Biosci. 2009;14:5239-5259.

    Not in our library10.2741/3595

  37. 37.
    Neuroinvasion and Inflammation in Viral Central Nervous System Infections · 2016
    No notice
  38. 38.

    Desforges M., Le Coupanec A., Stodola J.K., Meessen-Pinard M., Talbot P.J. Human coronaviruses: Viral and cellular factors involved in neuroinvasiveness and neuropathogenesis. Virus Res. 2014;194:145-158.

    Not in our library10.1016/j.virusres.2014.09.011

  39. 39.
    The choroid plexus—a multi-role player during infectious diseases of the CNS · 2015
    No notice
  40. 40.

    Kim W.K., Corey S., Alvarez X., Williams K. Monocyte/macrophage traffic in HIV and SIV encephalitis. J. Leukoc. Biol. 2003;74:650-656.

    Not in our library10.1189/jlb.0503207

  41. 41.

    Argyris E.G., Acheampong E., Wang F., Huang J., Chen K., Mukhtar M., Zhang H. The interferon-induced expression of APOBEC3G in human blood-brain barrier exerts a potent intrinsic immunity to block HIV-1 entry to central nervous system. Virology. 2007;367:440-451.

    Not in our library10.1016/j.virol.2007.06.010

  42. 42.

    Atluri V.S., Hidalgo M., Samikkannu T., Kurapati K.R., Jayant R.D., Sagar V., Nair M.P. Effect of human immunodeficiency virus on blood-brain barrier integrity and function: An update. Front. Cell Neurosci. 2015;9:212.

    Not in our library10.3389/fncel.2015.00212

  43. 43.

    Wang H., Sun J., Goldstein H. Human immunodeficiency virus type 1 infection increases the in vivo capacity of peripheral monocytes to cross the blood-brain barrier into the brain and the in vivo sensitivity of the blood-brain barrier to disruption by lipopolysaccharide. J. Virol. 2008;82:7591-7600.

    Not in our library10.1128/jvi.00768-08

  44. 44.

    Sellner J., Simon F., Meyding-Lamade U., Leib S.L. Herpes-simplex virus encephalitis is characterized by an early MMP-9 increase and collagen type IV degradation. Brain Res. 2006;1125:155-162.

    Not in our library10.1016/j.brainres.2006.09.093

  45. 45.

    Spindler K.R., Hsu T.H. Viral disruption of the blood-brain barrier. Trends Microbiol. 2012;20:282-290.

    Not in our library10.1016/j.tim.2012.03.009

  46. 46.

    Bentz G.L., Jarquin-Pardo M., Chan G., Smith M.S., Sinzger C., Yurochko A.D. Human cytomegalovirus (HCMV) infection of endothelial cells promotes naive monocyte extravasation and transfer of productive virus to enhance hematogenous dissemination of HCMV. J. Virol. 2006;80:11539-11555.

    Not in our library10.1128/jvi.01016-06

  47. 47.

    Chan G., Nogalski M.T., Stevenson E.V., Yurochko A.D. Human cytomegalovirus induction of a unique signalsome during viral entry into monocytes mediates distinct functional changes: A strategy for viral dissemination. J. Leukoc. Biol. 2012;92:743-752.

    Not in our library10.1189/jlb.0112040

  48. 48.

    Rhoades R.E., Tabor-Godwin J.M., Tsueng G., Feuer R. Enterovirus infections of the central nervous system. Virology. 2011;411:288-305.

    Not in our library10.1016/j.virol.2010.12.014

  49. 49.

    Feuer R., Mena I., Pagarigan R.R., Harkins S., Hassett D.E., Whitton J.L. Coxsackievirus B3 and the neonatal CNS: The roles of stem cells, developing neurons, and apoptosis in infection, viral dissemination, and disease. Am. J. Pathol. 2003;163:1379-1393.

    Not in our library10.1016/s0002-9440(10)63496-7

  50. 50.

    Neal J.W. Flaviviruses are neurotropic, but how do they invade the CNS? J. Infect. 2014;69:203-215.

    Not in our library10.1016/j.jinf.2014.05.010

  51. 51.
    A Mouse Model for Chikungunya: Young Age and Inefficient Type-I Interferon Signaling Are Risk Factors for Severe Disease · 2008
    No notice
  52. 52.

    Schneider H., Weber C.E., Schoeller J., Steinmann U., Borkowski J., Ishikawa H., Findeisen P., Adams O., Doerries R., Schwerk C., et al. Chemotaxis of T-cells after infection of human choroid plexus papilloma cells with Echovirus 30 in an in vitro model of the blood-cerebrospinal fluid barrier. Virus Res. 2012;170:66-74.

    Not in our library10.1016/j.virusres.2012.08.019

  53. 53.

    Halfhide C.P., Flanagan B.F., Brearey S.P., Hunt J.A., Fonceca A.M., McNamara P.S., Howarth D., Edwards S., Smyth R.L. Respiratory syncytial virus binds and undergoes transcription in neutrophils from the blood and airways of infants with severe bronchiolitis. J. Infect. Dis. 2011;204:451-458.

    Not in our library10.1093/infdis/jir280

  54. 54.

    Rohwedder A., Keminer O., Forster J., Schneider K., Schneider E., Werchau H. Detection of respiratory syncytial virus RNA in blood of neonates by polymerase chain reaction. J. Med. Virol. 1998;54:320-327.

    Not in our library10.1002/(sici)1096-9071(199804)54:4<320::aid-jmv13>3.0.co;2-j

  55. 55.

    Mathieu C., Pohl C., Szecsi J., Trajkovic-Bodennec S., Devergnas S., Raoul H., Cosset F.L., Gerlier D., Wild T.F., Horvat B. Nipah virus uses leukocytes for efficient dissemination within a host. J. Virol. 2011;85:7863-7871.

    Not in our library10.1128/jvi.00549-11

  56. 56.

    Escaffre O., Borisevich V., Rockx B. Pathogenesis of Hendra and Nipah virus infection in humans. J. Infect. Dev. Ctries. 2013;7:308-311.

    Not in our library10.3855/jidc.3648

  57. 57.

    Choi S.M., Xie H., Campbell A.P., Kuypers J., Leisenring W., Boudreault A.A., Englund J.A., Corey L., Boeckh M. Influenza viral RNA detection in blood as a marker to predict disease severity in hematopoietic cell transplant recipients. J. Infect. Dis. 2012;206:1872-1877.

    Not in our library10.1093/infdis/jis610

  58. 58.
    Clinical and virological factors associated with viremia in pandemic influenza A/H1N1/2009 virus infection. · 2011
    Not checked
  59. 59.

    Xu H., Yasui O., Tsuruoka H., Kuroda K., Hayashi K., Yamada A., Ishizaki T., Yamada Y., Watanabe T., Hosaka Y. Isolation of type B influenza virus from the blood of children. Clin. Infect. Dis. 1998;27:654-655.

    Not in our library10.1086/517146

  60. 60.

    Imamura T., Suzuki A., Lupisan S., Kamigaki T., Okamoto M., Roy C.N., Olveda R., Oshitani H. Detection of enterovirus 68 in serum from pediatric patients with pneumonia and their clinical outcomes. Influenza Other Respir. Viruses. 2014;8:21-24.

    Not in our library10.1111/irv.12206

  61. 61.

    Mori I. Transolfactory neuroinvasion by viruses threatens the human brain. Acta Virol. 2015;59:338-349.

    Not in our library10.4149/av_2015_04_338

  62. 62.

    Bryche B., Fretaud M., Saint-Albin Deliot A., Galloux M., Sedano L., Langevin C., Descamps D., Rameix-Welti M.A., Eleouet J.F., Le Goffic R., et al. Respiratory syncytial virus tropism for olfactory sensory neurons in mice. J. Neurochem. 2019;e14936.

    Not in our library10.1111/jnc.14936

  63. 63.

    Dups J., Middleton D., Yamada M., Monaghan P., Long F., Robinson R., Marsh G.A., Wang L.F. A new model for Hendra virus encephalitis in the mouse. PLoS ONE. 2012;7:e40308.

    Not in our library10.1371/journal.pone.0040308

  64. 64.

    Lochhead J.J., Kellohen K.L., Ronaldson P.T., Davis T.P. Distribution of insulin in trigeminal nerve and brain after intranasal administration. Sci. Rep. 2019;9:2621.

    Not in our library10.1038/s41598-019-39191-5

  65. 65.

    Lochhead J.J., Thorne R.G. Intranasal delivery of biologics to the central nervous system. Adv. Drug. Deliv. Rev. 2012;64:614-628.

    Not in our library10.1016/j.addr.2011.11.002

  66. 66.

    Driessen A.K., Farrell M.J., Mazzone S.B., McGovern A.E. Multiple neural circuits mediating airway sensations: Recent advances in the neurobiology of the urge-to-cough. Respir. Physiol. Neurobiol. 2016;226:115-120.

    Not in our library10.1016/j.resp.2015.09.017

  67. 67.

    Audrit K.J., Delventhal L., Aydin O., Nassenstein C. The nervous system of airways and its remodeling in inflammatory lung diseases. Cell Tissue Res. 2017;367:571-590.

    Not in our library10.1007/s00441-016-2559-7

  68. 68.

    Park C.H., Ishinaka M., Takada A., Kida H., Kimura T., Ochiai K., Umemura T. The invasion routes of neurovirulent A/Hong Kong/483/97 (H5N1) influenza virus into the central nervous system after respiratory infection in mice. Arch. Virol. 2002;147:1425-1436.

    Not in our library10.1007/s00705-001-0750-x

  69. 69.

    Matsuda K., Park C.H., Sunden Y., Kimura T., Ochiai K., Kida H., Umemura T. The vagus nerve is one route of transneural invasion for intranasally inoculated influenza a virus in mice. Vet. Pathol. 2004;41:101-107.

    Not in our library10.1354/vp.41-2-101

  70. 70.
    Management of Viral Central Nervous System Infections: A Primer for Clinicians · 2017
    Not checked
  71. 71.

    Kennedy P.G. Viral encephalitis: Causes, differential diagnosis, and management. J. Neurol. Neurosurg. Psychiatry. 2004;75:i10-i15.

    Not in our library10.1136/jnnp.2003.034280

  72. 72.

    Kennedy P.G. Viral encephalitis. J. Neurol. 2005;252:268-272.

    Not in our library10.1007/s00415-005-0770-7

  73. 73.
    Viral encephalitis: a practical review on diagnostic approach and treatment · 2020
    Not checked
  74. 74.

    Giraudon P., Bernard A. Inflammation in neuroviral diseases. J. Neural Transm. 2010;117:899-906.

    Not in our library10.1007/s00702-010-0402-y

  75. 75.

    Whitley R.J., Gnann J.W. Viral encephalitis: Familiar infections and emerging pathogens. Lancet. 2002;359:507-513.

    Not in our library10.1016/s0140-6736(02)07681-x

  76. 76.

    Koskiniemi M., Rautonen J., Lehtokoski-Lehtiniemi E., Vaheri A. Epidemiology of encephalitis in children: A 20-year survey. Ann. Neurol. 1991;29:492-497.

    Not in our library10.1002/ana.410290508

  77. 77.

    Hankins D.G., Rosekrans J.A. Overview, prevention, and treatment of rabies. Mayo Clin. Proc. 2004;79:671-676.

    Not in our library10.4065/79.5.671

  78. 78.

    Stahl J.P., Mailles A. Herpes simplex virus encephalitis update. Curr. Opin. Infect. Dis. 2019;32:239-243.

    Not in our library10.1097/qco.0000000000000554

  79. 79.

    Steiner I., Benninger F. Manifestations of Herpes Virus Infections in the Nervous System. Neurol. Clin. 2018;36:725-738.

    Not in our library10.1016/j.ncl.2018.06.005

  80. 80.

    Kennedy P.G., Chaudhuri A. Herpes simplex encephalitis. J. Neurol. Neurosurg Psychiatry. 2002;73:237-238.

    Not in our library10.1136/jnnp.73.3.237

  81. 81.

    Aurelian L. HSV-induced apoptosis in herpes encephalitis. Curr. Top. Microbiol. Immunol. 2005;289:79-111.

    Not in our library10.1007/3-540-27320-4_4

  82. 82.

    Beckham J.D., Tyler K.L. Arbovirus Infections. Continuum (Minneap Minn). 2015;21:1599-1611.

    Not in our library10.1212/con.0000000000000240

  83. 83.
    Neurological Sequelae Resulting from Encephalitic Alphavirus Infection · 2016
    No notice
  84. 84.

    Yun S.I., Lee Y.M. Zika virus: An emerging flavivirus. J. Microbiol. 2017;55:204-219.

    Not in our library10.1007/s12275-017-7063-6

  85. 85.

    Ritter J.M., Martines R.B., Zaki S.R. Zika Virus: Pathology from the Pandemic. Arch. Pathol. Lab. Med. 2017;141:49-59.

    Not in our library10.5858/arpa.2016-0397-sa

  86. 86.

    Sips G.J., Wilschut J., Smit J.M. Neuroinvasive flavivirus infections. Rev. Med. Virol. 2012;22:69-87.

    Not in our library10.1002/rmv.712

  87. 87.

    Mackenzie J.S., Gubler D.J., Petersen L.R. Emerging flaviviruses: The spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nat. Med. 2004;10:S98-S109.

    Not in our library10.1038/nm1144

  88. 88.

    Mueller S., Wimmer E., Cello J. Poliovirus and poliomyelitis: A tale of guts, brains, and an accidental event. Virus Res. 2005;111:175-193.

    Not in our library10.1016/j.virusres.2005.04.008

  89. 89.

    Mattson M.P., Haughey N.J., Nath A. Cell death in HIV dementia. Cell Death Differ. 2005;12:893-904.

    Not in our library10.1038/sj.cdd.4401577

  90. 90.

    Pandey H.S., Seth P. Friends Turn Foe-Astrocytes Contribute to Neuronal Damage in NeuroAIDS. J. Mol. Neurosci. 2019;69:286-297.

    Not in our library10.1007/s12031-019-01357-1

  91. 91.

    Balcom E.F., Roda W.C., Cohen E.A., Li M.Y., Power C. HIV-1 persistence in the central nervous system: Viral and host determinants during antiretroviral therapy. Curr. Opin. Virol. 2019;38:54-62.

    Not in our library10.1016/j.coviro.2019.06.004

  92. 92.

    Nath A., Berger J. HIV Dementia. Curr. Treat. Options Neurol. 2004;6:139-151.

    Not in our library10.1007/s11940-004-0023-6

  93. 93.

    Gordon J., Gallia G.L., Del Valle L., Amini S., Khalili K. Human polyomavirus JCV and expression of myelin genes. J. Neurovirol. 2000;6:S92-S97.

    Not in our library

  94. 94.

    Weissert R. Progressive multifocal leukoencephalopathy. J. Neuroimmunol. 2011;231:73-77.

    Not in our library10.1016/j.jneuroim.2010.09.021

  95. 95.

    Wollebo H.S., White M.K., Gordon J., Berger J.R., Khalili K. Persistence and pathogenesis of the neurotropic polyomavirus JC. Ann. Neurol. 2015;77:560-570.

    Not in our library10.1002/ana.24371

  96. 96.

    Kaplan J.E., Osame M., Kubota H., Igata A., Nishitani H., Maeda Y., Khabbaz R.F., Janssen R.S. The risk of development of HTLV-I-associated myelopathy/tropical spastic paraparesis among persons infected with HTLV-I. J. Acquir. Immune Defic. Syndr. 1990;3:1096-1101.

    Not in our library

  97. 97.

    Schoini P., Karampitsakos T., Avdikou M., Athanasopoulou A., Tsoukalas G., Tzouvelekis A. Measles pneumonitis. Adv. Respir. Med. 2019;87:63-67.

    Not in our library10.5603/arm.a2019.0010

  98. 98.

    Albarello F., Cristofaro M., Busi Rizzi E., Giancola M.L., Nicastri E., Schinina V. Pulmonary measles disease: Old and new imaging tools. Radiol. Med. 2018;123:935-943.

    Not in our library10.1007/s11547-018-0919-y

  99. 99.

    O’Donnell L.A., Rall G.F. Blue moon neurovirology: The merits of studying rare CNS diseases of viral origin. J. Neuroimmune Pharmacol. 2010;5:443-455.

    Not in our library10.1007/s11481-010-9200-4

  100. 100.

    Wilson M.R., Ludlow M., Duprex W.P., Singh S.K., Ruzek D. Human Paramyxoviruses and Infections of the Central Nervous System. Neuroviral Infections. RNA Viruses and Retroviruses. 2013;341-372.

    Not in our library

  101. 101.

    Leibovitch E.C., Jacobson S. Viruses in chronic progressive neurologic disease. Mult. Scler. 2018;24:48-52.

    Not in our library10.1177/1352458517737392

  102. 102.

    Itzhaki R.F., Dobson C.B., Wozniak M.A. Herpes simplex virus type 1 and Alzheimer’s disease. Ann. Neurol. 2004;55:299-300.

    Not in our library10.1002/ana.10852

  103. 103.
    Neurotropic virus infections as the cause of immediate and delayed neuropathology · 2015
    No notice
  104. 104.

    Majde J.A. Neuroinflammation resulting from covert brain invasion by common viruses-a potential role in local and global neurodegeneration. Med. Hypotheses. 2010;75:204-213.

    Not in our library10.1016/j.mehy.2010.02.023

  105. 105.

    Lebov J.F., Brown L.M., MacDonald P.D.M., Robertson K., Bowman N.M., Hooper S.R., Becker-Dreps S. Review: Evidence of Neurological Sequelae in Children With Acquired Zika Virus Infection. Pediatr. Neurol. 2018;85:16-20.

    Not in our library10.1016/j.pediatrneurol.2018.03.001

  106. 106.

    Weatherhead J.E., Miller V.E., Garcia M.N., Hasbun R., Salazar L., Dimachkie M.M., Murray K.O. Long-term neurological outcomes in West Nile virus-infected patients: An observational study. Am. J. Trop. Med. Hyg. 2015;92:1006-1012.

    Not in our library10.4269/ajtmh.14-0616

  107. 107.

    Athar P., Hasbun R., Nolan M.S., Salazar L., Woods S.P., Sheikh K., Murray K.O. Long-term neuromuscular outcomes of west nile virus infection: A clinical and electromyographic evaluation of patients with a history of infection. Muscle Nerve. 2018;57:77-82.

    Not in our library10.1002/mus.25660

  108. 108.

    Edridge A.W.D., Deijs M., van Zeggeren I.E., Kinsella C.M., Jebbink M.F., Bakker M., van de Beek D., Brouwer M.C., van der Hoek L. Viral Metagenomics on Cerebrospinal Fluid. Genes. 2019;10:332.

    Not in our library10.3390/genes10050332

  109. 109.

    Granerod J., Cunningham R., Zuckerman M., Mutton K., Davies N.W., Walsh A.L., Ward K.N., Hilton D.A., Ambrose H.E., Clewley J.P., et al. Causality in acute encephalitis: Defining aetiologies. Epidemiol. Infect. 2010;138:783-800.

    Not in our library10.1017/s0950268810000725

  110. 110.

    Granerod J., Tam C.C., Crowcroft N.S., Davies N.W., Borchert M., Thomas S.L. Challenge of the unknown. A systematic review of acute encephalitis in non-outbreak situations. Neurology. 2010;75:924-932.

    Not in our library10.1212/wnl.0b013e3181f11d65

  111. 111.

    Schibler M., Brito F., Zanella M.C., Zdobnov E.M., Laubscher F., L’Huillier A.G., Ambrosioni J., Wagner N., Posfay-Barbe K.M., Docquier M., et al. Viral Sequences Detection by High-Throughput Sequencing in Cerebrospinal Fluid of Individuals with and without Central Nervous System Disease. Genes. 2019;10:625.

    Not in our library10.3390/genes10080625

  112. 112.

    King A.M.Q., Lefkowitz E.J., Mushegian A.R., Adams M.J., Dutilh B.E., Gorbalenya A.E., Harrach B., Harrison R.L., Junglen S., Knowles N.J., et al. Changes to taxonomy and the International Code of Virus Classification and Nomenclature ratified by the International Committee on Taxonomy of Viruses (2018). Arch. Virol. 2018;163:2601-2631.

    Not in our library10.1007/s00705-018-3847-1

  113. 113.

    Nair H., Nokes D.J., Gessner B.D., Dherani M., Madhi S.A., Singleton R.J., O’Brien K.L., Roca A., Wright P.F., Bruce N., et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: A systematic review and meta-analysis. Lancet. 2010;375:1545-1555.

    Not in our library10.1016/s0140-6736(10)60206-1

  114. 114.

    Stensballe L.G., Devasundaram J.K., Simoes E.A. Respiratory syncytial virus epidemics: The ups and downs of a seasonal virus. Pediatr. Infect. Dis. J. 2003;22:S21-S32.

    Not in our library10.1097/01.inf.0000053882.70365.c9

  115. 115.

    Nam H.H., Ison M.G. Respiratory syncytial virus infection in adults. BMJ. 2019;366.

    Not in our library10.1136/bmj.l5021

  116. 116.

    Picone S., Mondi V., Di Palma F., Martini L., Paolillo P. Neonatal Encephalopathy and SIADH during RSV Infection. Am. J. Perinatol. 2019;36:S106-S109.

    Not in our library10.1055/s-0039-1692132

  117. 117.

    Bohmwald K., Espinoza J.A., Gonzalez P.A., Bueno S.M., Riedel C.A., Kalergis A.M. Central nervous system alterations caused by infection with the human respiratory syncytial virus. Rev. Med. Virol. 2014;24:407-419.

    Not in our library10.1002/rmv.1813

  118. 118.

    Morichi S., Kawashima H., Ioi H., Yamanaka G., Kashiwagi Y., Hoshika A., Nakayama T., Watanabe Y. Classification of acute encephalopathy in respiratory syncytial virus infection. J. Infect. Chemother. 2011;17:776-781.

    Not in our library10.1007/s10156-011-0259-5

  119. 119.

    Kawashima H., Ioi H., Ushio M., Yamanaka G., Matsumoto S., Nakayama T. Cerebrospinal fluid analysis in children with seizures from respiratory syncytial virus infection. Scand. J. Infect. Dis. 2009;41:228-231.

    Not in our library10.1080/00365540802669543

  120. 120.

    Zlateva K.T., Van Ranst M. Detection of subgroup B respiratory syncytial virus in the cerebrospinal fluid of a patient with respiratory syncytial virus pneumonia. Pediatr. Infect. Dis. J. 2004;23:1065-1066.

    Not in our library10.1097/01.inf.0000143654.12493.c9

  121. 121.

    Millichap J.J., Wainwright M.S. Neurological complications of respiratory syncytial virus infection: Case series and review of literature. J. Child. Neurol. 2009;24:1499-1503.

    Not in our library10.1177/0883073808331362

  122. 122.

    Ng Y.T., Cox C., Atkins J., Butler I.J. Encephalopathy associated with respiratory syncytial virus bronchiolitis. J. Child. Neurol. 2001;16:105-108.

    Not in our library10.1177/088307380101600207

  123. 123.

    Hirayama K., Sakazaki H., Murakami S., Yonezawa S., Fujimoto K., Seto T., Tanaka K., Hattori H., Matsuoka O., Murata R. Sequential MRI, SPECT and PET in respiratory syncytial virus encephalitis. Pediatr. Radiol. 1999;29:282-286.

    Not in our library10.1007/s002470050589

  124. 124.

    Morton R.E., Dinwiddie R., Marshall W.C., Matthew D.J. Respiratory syncytial virus infection causing neurological disorder in neonates. Lancet. 1981;1:1426-1427.

    Not in our library10.1016/s0140-6736(81)92609-x

  125. 125.

    Cappel R., Thiry L., Clinet G. Viral antibodies in the CSF after acute CNS infections. Arch. Neurol. 1975;32:629-631.

    Not in our library10.1001/archneur.1975.00490510085008

  126. 126.

    Wallace S.J., Zealley H. Neurological, electroencephalographic, and virological findings in febrile cheldren. Arch. Dis. Child. 1970;45:611-623.

    Not in our library10.1136/adc.45.243.611

  127. 127.

    Espinoza J.A., Bohmwald K., Cespedes P.F., Gomez R.S., Riquelme S.A., Cortes C.M., Valenzuela J.A., Sandoval R.A., Pancetti F.C., Bueno S.M., et al. Impaired learning resulting from respiratory syncytial virus infection. Proc. Natl. Acad. Sci. USA. 2013;110:9112-9117.

    Not in our library10.1073/pnas.1217508110

  128. 128.

    Van den Hoogen B.G., de Jong J.C., Groen J., Kuiken T., de Groot R., Fouchier R.A., Osterhaus A.D. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat. Med. 2001;7:719-724.

    Not in our library10.1038/89098

  129. 129.

    Edwards K.M., Zhu Y., Griffin M.R., Weinberg G.A., Hall C.B., Szilagyi P.G., Staat M.A., Iwane M., Prill M.M., Williams J.V., et al. Burden of human metapneumovirus infection in young children. N. Engl. J. Med. 2013;368:633-643.

    Not in our library10.1056/nejmoa1204630

  130. 130.

    Jeannet N., van den Hoogen B.G., Schefold J.C., Suter-Riniker F., Sommerstein R. Cerebrospinal Fluid Findings in an Adult with Human Metapneumovirus-Associated Encephalitis. Emerg. Infect. Dis. 2017;23:370.

    Not in our library10.3201/eid2302.161337

  131. 131.

    Fok A., Mateevici C., Lin B., Chandra R.V., Chong V.H. Encephalitis-Associated Human Metapneumovirus Pneumonia in Adult, Australia. Emerg. Infect. Dis. 2015;21:2074-2076.

    Not in our library10.3201/eid2111.150608

  132. 132.

    Tan Y.L., Wee T.C. Adult human metapneumovirus encephalitis: A case report highlighting challenges in clinical management and functional outcome. Med. J. Malays. 2017;72:372-373.

    Not in our library

  133. 133.

    Schildgen O., Glatzel T., Geikowski T., Scheibner B., Matz B., Bindl L., Born M., Viazov S., Wilkesmann A., Knopfle G., et al. Human metapneumovirus RNA in encephalitis patient. Emerg. Infect. Dis. 2005;11:467-470.

    Not in our library10.3201/eid1103.040676

  134. 134.

    Sanchez Fernandez I., Rebollo Polo M., Munoz-Almagro C., Monfort Carretero L., Fernandez Urena S., Rueda Munoz A., Colome Roura R., Perez Duenas B. Human Metapneumovirus in the Cerebrospinal Fluid of a Patient With Acute Encephalitis. Arch. Neurol. 2012;69:649-652.

    Not in our library10.1001/archneurol.2011.1094

  135. 135.

    Dawes B.E., Freiberg A.N. Henipavirus infection of the central nervous system. Pathog Dis. 2019;77.

    Not in our library10.1093/femspd/ftz023

  136. 136.

    Escaffre O., Borisevich V., Carmical J.R., Prusak D., Prescott J., Feldmann H., Rockx B. Henipavirus pathogenesis in human respiratory epithelial cells. J. Virol. 2013;87:3284-3294.

    Not in our library10.1128/jvi.02576-12

  137. 137.

    Ochani R.K., Batra S., Shaikh A., Asad A. Nipah virus-the rising epidemic: A review. Infez. Med. 2019;27:117-127.

    Not in our library

  138. 138.

    Ang B.S.P., Lim T.C.C., Wang L. Nipah Virus Infection. J. Clin. Microbiol. 2018;56:e01875-17.

    Not in our library10.1128/jcm.01875-17

  139. 139.

    Wong K.T., Robertson T., Ong B.B., Chong J.W., Yaiw K.C., Wang L.F., Ansford A.J., Tannenberg A. Human Hendra virus infection causes acute and relapsing encephalitis. Neuropathol. Appl. Neurobiol. 2009;35:296-305.

    Not in our library10.1111/j.1365-2990.2008.00991.x

  140. 140.

    Wong K.T., Shieh W.J., Kumar S., Norain K., Abdullah W., Guarner J., Goldsmith C.S., Chua K.B., Lam S.K., Tan C.T., et al. Nipah virus infection: Pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am. J. Pathol. 2002;161:2153-2167.

    Not in our library10.1016/s0002-9440(10)64493-8

  141. 141.

    Sejvar J.J., Hossain J., Saha S.K., Gurley E.S., Banu S., Hamadani J.D., Faiz M.A., Siddiqui F.M., Mohammad Q.D., Mollah A.H., et al. Long-term neurological and functional outcome in Nipah virus infection. Ann. Neurol. 2007;62:235-242.

    Not in our library10.1002/ana.21178

  142. 142.

    Ng B.Y., Lim C.C., Yeoh A., Lee W.L. Neuropsychiatric sequelae of Nipah virus encephalitis. J. Neuropsychiatry Clin. Neurosci. 2004;16:500-504.

    Not in our library10.1176/jnp.16.4.500

  143. 143.

    Wong K.T., Tan C.T. Clinical and pathological manifestations of human henipavirus infection. Curr. Top. Microbiol. Immunol. 2012;359:95-104.

    Not in our library10.1007/82_2012_205

  144. 144.

    Munster V.J., Prescott J.B., Bushmaker T., Long D., Rosenke R., Thomas T., Scott D., Fischer E.R., Feldmann H., de Wit E. Rapid Nipah virus entry into the central nervous system of hamsters via the olfactory route. Sci. Rep. 2012;2:736.

    Not in our library10.1038/srep00736

  145. 145.

    Liu J., Coffin K.M., Johnston S.C., Babka A.M., Bell T.M., Long S.Y., Honko A.N., Kuhn J.H., Zeng X. Nipah virus persists in the brains of nonhuman primate survivors. JCI Insight. 2019;4.

    Not in our library10.1172/jci.insight.129629

  146. 146.

    Tan C.T., Goh K.J., Wong K.T., Sarji S.A., Chua K.B., Chew N.K., Murugasu P., Loh Y.L., Chong H.T., Tan K.S., et al. Relapsed and late-onset Nipah encephalitis. Ann. Neurol. 2002;51:703-708.

    Not in our library10.1002/ana.10212

  147. 147.

    Kuiken T., Riteau B., Fouchier R.A., Rimmelzwaan G.F. Pathogenesis of influenza virus infections: The good, the bad and the ugly. Curr. Opin. Virol. 2012;2:276-286.

    Not in our library10.1016/j.coviro.2012.02.013

  148. 148.

    Asha K., Kumar B. Emerging Influenza D Virus Threat: What We Know so Far! J. Clin. Med. 2019;8:192.

    Not in our library10.3390/jcm8020192

  149. 149.

    Nicholson K.G., Wood J.M., Zambon M. Influenza. Lancet. 2003;362:1733-1745.

    Not in our library10.1016/s0140-6736(03)14854-4

  150. 150.
    Neurologic Complications of Influenza B Virus Infection in Adults, Romania · 2017
    Not checked
  151. 151.

    Jang H., Boltz D., Sturm-Ramirez K., Shepherd K.R., Jiao Y., Webster R., Smeyne R.J. Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration. Proc. Natl. Acad. Sci. USA. 2009;106:14063-14068.

    Not in our library10.1073/pnas.0900096106

  152. 152.

    Kuiken T., Taubenberger J.K. Pathology of human influenza revisited. Vaccine. 2008;26:D59-D66.

    Not in our library10.1016/j.vaccine.2008.07.025

  153. 153.

    Sivadon-Tardy V., Orlikowski D., Porcher R., Sharshar T., Durand M.C., Enouf V., Rozenberg F., Caudie C., Annane D., van der Werf S., et al. Guillain-Barre syndrome and influenza virus infection. Clin. Infect. Dis. 2009;48:48-56.

    Not in our library10.1086/594124

  154. 154.

    Millichap J.G., Millichap J.J. Role of viral infections in the etiology of febrile seizures. Pediatr. Neurol. 2006;35:165-172.

    Not in our library10.1016/j.pediatrneurol.2006.06.004

  155. 155.

    Ozkale Y., Erol I., Ozkale M., Demir S., Alehan F. Acute disseminated encephalomyelitis associated with influenza A H1N1 infection. Pediatr. Neurol. 2012;47:62-64.

    Not in our library10.1016/j.pediatrneurol.2012.03.019

  156. 156.

    Toovey S. Influenza-associated central nervous system dysfunction: A literature review. Travel Med. Infect. Dis. 2008;6:114-124.

    Not in our library10.1016/j.tmaid.2008.03.003

  157. 157.

    Wang G.F., Li W., Li K. Acute encephalopathy and encephalitis caused by influenza virus infection. Curr. Opin. Neurol. 2010;23:305-311.

    Not in our library10.1097/wco.0b013e328338f6c9

  158. 158.

    Zeng H., Quinet S., Huang W., Gan Y., Han C., He Y., Wang Y. Clinical and MRI features of neurological complications after influenza A (H1N1) infection in critically ill children. Pediatr. Radiol. 2013;43:1182-1189.

    Not in our library10.1007/s00247-013-2682-5

  159. 159.

    Shinya K., Makino A., Hatta M., Watanabe S., Kim J.H., Hatta Y., Gao P., Ozawa M., Le Q.M., Kawaoka Y. Subclinical brain injury caused by H5N1 influenza virus infection. J. Virol. 2011;85:5202-5207.

    Not in our library10.1128/jvi.00239-11

  160. 160.

    Hosseini S., Wilk E., Michaelsen-Preusse K., Gerhauser I., Baumgartner W., Geffers R., Schughart K., Korte M. Long-Term Neuroinflammation Induced by Influenza A Virus Infection and the Impact on Hippocampal Neuron Morphology and Function. J. Neurosci. 2018;38:3060-3080.

    Not in our library10.1523/jneurosci.1740-17.2018

  161. 161.

    Beraki S., Aronsson F., Karlsson H., Ogren S.O., Kristensson K. Influenza A virus infection causes alterations in expression of synaptic regulatory genes combined with changes in cognitive and emotional behaviors in mice. Mol. Psychiatry. 2005;10:299-308.

    Not in our library10.1038/sj.mp.4001545

  162. 162.

    Jurgens H.A., Amancherla K., Johnson R.W. Influenza infection induces neuroinflammation, alters hippocampal neuron morphology, and impairs cognition in adult mice. J. Neurosci. 2012;32:3958-3968.

    Not in our library10.1523/jneurosci.6389-11.2012

  163. 163.

    Chen Q., Liu Y., Lu A., Ni K., Xiang Z., Wen K., Tu W. Influenza virus infection exacerbates experimental autoimmune encephalomyelitis disease by promoting type I T cells infiltration into central nervous system. J. Autoimmun. 2017;77:1-10.

    Not in our library10.1016/j.jaut.2016.10.006

  164. 164.

    Oikonen M., Laaksonen M., Aalto V., Ilonen J., Salonen R., Eralinna J.P., Panelius M., Salmi A. Temporal relationship between environmental influenza A and Epstein-Barr viral infections and high multiple sclerosis relapse occurrence. Mult. Scler. 2011;17:672-680.

    Not in our library10.1177/1352458510394397

  165. 165.

    Edwards S., Zvartau M., Clarke H., Irving W., Blumhardt L.D. Clinical relapses and disease activity on magnetic resonance imaging associated with viral upper respiratory tract infections in multiple sclerosis. J. Neurol. Neurosurg Psychiatry. 1998;64:736-741.

    Not in our library10.1136/jnnp.64.6.736

  166. 166.

    Andres C., Vila J., Gimferrer L., Pinana M., Esperalba J., Codina M.G., Barnes M., Martin M.C., Fuentes F., Rubio S., et al. Surveillance of enteroviruses from paediatric patients attended at a tertiary hospital in Catalonia from 2014 to 2017. J. Clin. Virol. 2019;110:29-35.

    Not in our library10.1016/j.jcv.2018.11.004

  167. 167.

    Rao S., Messacar K., Torok M.R., Rick A.M., Holzberg J., Montano A., Bagdure D., Curtis D.J., Oberste M.S., Nix W.A., et al. Enterovirus D68 in Critically Ill Children: A Comparison With Pandemic H1N1 Influenza. Pediatr. Crit. Care Med. 2016;17:1023-1031.

    Not in our library10.1097/pcc.0000000000000922

  168. 168.
    Innate Immunity Evasion by Enteroviruses: Insights into Virus-Host Interaction · 2016
    Not checked
  169. 169.

    Tebruegge M., Curtis N. Enterovirus infections in neonates. Semin. Fetal Neonatal Med. 2009;14:222-227.

    Not in our library10.1016/j.siny.2009.02.002

  170. 170.

    Hazama K., Shiihara T., Tsukagoshi H., Matsushige T., Dowa Y., Watanabe M. Rhinovirus-associated acute encephalitis/encephalopathy and cerebellitis. Brain Dev. 2019;41:551-554.

    Not in our library10.1016/j.braindev.2019.02.014

  171. 171.

    Anastasina M., Domanska A., Palm K., Butcher S. Human picornaviruses associated with neurological diseases and their neutralization by antibodies. J. Gen. Virol. 2017;98:1145-1158.

    Not in our library10.1099/jgv.0.000780

  172. 172.

    Helfferich J., Knoester M., Van Leer-Buter C.C., Neuteboom R.F., Meiners L.C., Niesters H.G., Brouwer O.F. Acute flaccid myelitis and enterovirus D68: Lessons from the past and present. Eur. J. Pediatr. 2019;178:1305-1315.

    Not in our library10.1007/s00431-019-03435-3

  173. 173.

    Christy A., Messacar K. Acute Flaccid Myelitis Associated With Enterovirus D68: A Review. J. Child. Neurol. 2019;34:511-516.

    Not in our library10.1177/0883073819838376

  174. 174.

    Khan F. Enterovirus D68: Acute respiratory illness and the 2014 outbreak. Emerg. Med. Clin. N. Am. 2015;33:e19-e32.

    Not in our library10.1016/j.emc.2014.12.011

  175. 175.

    Pons-Salort M., Parker E.P., Grassly N.C. The epidemiology of non-polio enteroviruses: Recent advances and outstanding questions. Curr. Opin. Infect. Dis. 2015;28:479-487.

    Not in our library10.1097/qco.0000000000000187

  176. 176.

    Brian D.A., Baric R.S. Coronavirus genome structure and replication. Curr. Top. Microbiol. Immunol. 2005;287:1-30.

    Not in our library10.1007/3-540-26765-4_1

  177. 177.

    Greig A.S., Mitchell D., Corner A.H., Bannister G.L., Meads E.B., Julian R.J. A Hemagglutinating Virus Producing Encephalomyelitis in Baby Pigs. Can. J. Comp. Med. Vet. Sci. 1962;26:49-56.

    Not in our library

  178. 178.

    Foley J.E., Lapointe J.M., Koblik P., Poland A., Pedersen N.C. Diagnostic features of clinical neurologic feline infectious peritonitis. J. Vet. Intern. Med. 1998;12:415-423.

    Not in our library10.1111/j.1939-1676.1998.tb02144.x

  179. 179.

    Foley J.E., Rand C., Leutenegger C. Inflammation and changes in cytokine levels in neurological feline infectious peritonitis. J. Feline Med. Surg. 2003;5:313-322.

    Not in our library10.1016/s1098-612x(03)00048-2

  180. 180.

    Lampert P.W., Sims J.K., Kniazeff A.J. Mechanism of demyelination in JHM virus encephalomyelitis. Electron microscopic studies. Acta Neuropathol. 1973;24:76-85.

    Not in our library10.1007/bf00691421

  181. 181.

    Bender S.J., Weiss S.R. Pathogenesis of murine coronavirus in the central nervous system. J. Neuroimmune Pharmacol. Off. J. Soc. NeuroImmune Pharmacol. 2010;5:336-354.

    Not in our library10.1007/s11481-010-9202-2

  182. 182.

    Cowley T.J., Weiss S.R. Murine coronavirus neuropathogenesis: Determinants of virulence. J. Neurovirology. 2010;16:427-434.

    Not in our library10.1007/bf03210848

  183. 183.

    Hosking M.P., Lane T.E. The pathogenesis of murine coronavirus infection of the central nervous system. Crit. Rev. Immunol. 2010;30:119-130.

    Not in our library10.1615/critrevimmunol.v30.i2.20

  184. 184.

    Myint S.H., Siddell S.G. Human Coronavirus Infections. The Coronaviridae. 1995;389-401.

    Not in our library

  185. 185.

    Tyrrell D.A., Bynoe M.L. Cultivation of a Novel Type of Common-Cold Virus in Organ Cultures. Br. Med. J. 1965;1:1467-1470.

    Not in our library10.1136/bmj.1.5448.1467

  186. 186.

    Hamre D., Procknow J.J. A new virus isolated from the human respiratory tract. Proc. Soc. Exp. Biol. Med. 1966;121:190-193.

    Not in our library10.3181/00379727-121-30734

  187. 187.

    McIntosh K., Becker W.B., Chanock R.M. Growth in suckling-mouse brain of “IBV-like” viruses from patients with upper respiratory tract disease. Proc. Natl. Acad. Sci. USA. 1967;58:2268-2273.

    Not in our library10.1073/pnas.58.6.2268

  188. 188.

    Drosten C., Gunther S., Preiser W., van der Werf S., Brodt H.R., Becker S., Rabenau H., Panning M., Kolesnikova L., Fouchier R.A., et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 2003;348:1967-1976.

    Not in our library10.1056/nejmoa030747

  189. 189.

    Fouchier R.A., Kuiken T., Schutten M., van Amerongen G., van Doornum G.J., van den Hoogen B.G., Peiris M., Lim W., Stohr K., Osterhaus A.D. Aetiology: Koch’s postulates fulfilled for SARS virus. Nature. 2003;423:240.

    Not in our library10.1038/423240a

  190. 190.

    Ksiazek T.G., Erdman D., Goldsmith C.S., Zaki S.R., Peret T., Emery S., Tong S., Urbani C., Comer J.A., Lim W., et al. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 2003;348:1953-1966.

    Not in our library10.1056/nejmoa030781

  191. 191.

    Van der Hoek L., Pyrc K., Jebbink M.F., Vermeulen-Oost W., Berkhout R.J., Wolthers K.C., Wertheim-van Dillen P.M., Kaandorp J., Spaargaren J., Berkhout B. Identification of a new human coronavirus. Nat. Med. 2004;10:368-373.

    Not in our library10.1038/nm1024

  192. 192.

    Woo P.C., Lau S.K., Chu C.M., Chan K.H., Tsoi H.W., Huang Y., Wong B.H., Poon R.W., Cai J.J., Luk W.K., et al. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J. Virol. 2005;79:884-895.

    Not in our library10.1128/jvi.79.2.884-895.2005

  193. 193.

    Zaki A.M., van Boheemen S., Bestebroer T.M., Osterhaus A.D., Fouchier R.A. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 2012;367:1814-1820.

    Not in our library10.1056/nejmoa1211721

  194. 194.

    Cabeca T.K., Granato C., Bellei N. Epidemiological and clinical features of human coronavirus infections among different subsets of patients. Influenza Other Respir. Viruses. 2013;7:1040-1047.

    Not in our library10.1111/irv.12101

  195. 195.

    Gaunt E.R., Hardie A., Claas E.C., Simmonds P., Templeton K.E. Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method. J. Clin. Microbiol. 2010;48:2940-2947.

    Not in our library10.1128/jcm.00636-10

  196. 196.

    Larson H.E., Reed S.E., Tyrrell D.A. Isolation of rhinoviruses and coronaviruses from 38 colds in adults. J. Med. Virol. 1980;5:221-229.

    Not in our library10.1002/jmv.1890050306

  197. 197.

    Chiu S.S., Chan K.H., Chu K.W., Kwan S.W., Guan Y., Poon L.L., Peiris J.S. Human coronavirus NL63 infection and other coronavirus infections in children hospitalized with acute respiratory disease in Hong Kong, China. Clin. Infect. Dis. 2005;40:1721-1729.

    Not in our library10.1086/430301

  198. 198.
    Co-circulation of Four Human Coronaviruses (HCoVs) in Queensland Children with Acute Respiratory Tract Illnesses in 2004 · 2012
    Not checked
  199. 199.

    Theamboonlers A., Samransamruajkit R., Thongme C., Amonsin A., Chongsrisawat V., Poovorawan Y. Human coronavirus infection among children with acute lower respiratory tract infection in Thailand. Intervirology. 2007;50:71-77.

    Not in our library10.1159/000097392

  200. 200.

    Oong X.Y., Ng K.T., Takebe Y., Ng L.J., Chan K.G., Chook J.B., Kamarulzaman A., Tee K.K. Identification and evolutionary dynamics of two novel human coronavirus OC43 genotypes associated with acute respiratory infections: Phylogenetic, spatiotemporal and transmission network analyses. Emerg. Microbes Infect. 2017;6:e3.

    Not in our library10.1038/emi.2016.132

  201. 201.

    Zhang Y., Li J., Xiao Y., Zhang J., Wang Y., Chen L., Paranhos-Baccala G., Ren L., Wang J. Genotype shift in human coronavirus OC43 and emergence of a novel genotype by natural recombination. J. Infect. 2015;70:641-650.

    Not in our library10.1016/j.jinf.2014.12.005

  202. 202.

    Dominguez S.R., Sims G.E., Wentworth D.E., Halpin R.A., Robinson C.C., Town C.D., Holmes K.V. Genomic analysis of 16 Colorado human NL63 coronaviruses identifies a new genotype, high sequence diversity in the N-terminal domain of the spike gene and evidence of recombination. J. Gen. Virol. 2012;93:2387-2398.

    Not in our library10.1099/vir.0.044628-0

  203. 203.

    Gerna G., Campanini G., Rovida F., Percivalle E., Sarasini A., Marchi A., Baldanti F. Genetic variability of human coronavirus OC43-, 229E-, and NL63-like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients. J. Med. Virol. 2006;78:938-949.

    Not in our library10.1002/jmv.20645

  204. 204.

    Lau S.K., Lee P., Tsang A.K., Yip C.C., Tse H., Lee R.A., So L.Y., Lau Y.L., Chan K.H., Woo P.C., et al. Molecular epidemiology of human coronavirus OC43 reveals evolution of different genotypes over time and recent emergence of a novel genotype due to natural recombination. J. Virol. 2011;85:11325-11337.

    Not in our library10.1128/jvi.05512-11

  205. 205.

    Vabret A., Dina J., Mourez T., Gouarin S., Petitjean J., van der Werf S., Freymuth F. Inter- and intra-variant genetic heterogeneity of human coronavirus OC43 strains in France. J. Gen. Virol. 2006;87:3349-3353.

    Not in our library10.1099/vir.0.82065-0

  206. 206.

    Vijgen L., Lemey P., Keyaerts E., Van Ranst M. Genetic variability of human respiratory coronavirus OC43. J. Virol. 2005;79:3223-3224.

    Not in our library10.1128/jvi.79.5.3223-3225.2005

  207. 207.

    Woo P.C., Lau S.K., Yip C.C., Huang Y., Tsoi H.W., Chan K.H., Yuen K.Y. Comparative analysis of 22 coronavirus HKU1 genomes reveals a novel genotype and evidence of natural recombination in coronavirus HKU1. J. Virol. 2006;80:7136-7145.

    Not in our library10.1128/jvi.00509-06

  208. 208.

    Talbot P.J., Jacomy H., Desforges M., Perlman S., Gallagher T., Snijder E.J. Pathogenesis of Human Coronaviruses other than Severe Acute Respiratory Syndrome Coronavirus. Nidoviruses. 2008;313-324.

    Not in our library

  209. 209.

    Greenberg S.B. Update on Human Rhinovirus and Coronavirus Infections. Semin. Respir. Crit. Care Med. 2016;37:555-571.

    Not in our library10.1055/s-0036-1584797

  210. 210.

    Lee J., Storch G.A. Characterization of human coronavirus OC43 and human coronavirus NL63 infections among hospitalized children <5 years of age. Pediatr. Infect. Dis. J. 2014;33:814-820.

    Not in our library10.1097/inf.0000000000000292

  211. 211.

    Self W.H., Williams D.J., Zhu Y., Ampofo K., Pavia A.T., Chappell J.D., Hymas W.C., Stockmann C., Bramley A.M., Schneider E., et al. Respiratory Viral Detection in Children and Adults: Comparing Asymptomatic Controls and Patients With Community-Acquired Pneumonia. J. Infect. Dis. 2016;213:584-591.

    Not in our library10.1093/infdis/jiv323

  212. 212.

    Ogimi C., Englund J.A., Bradford M.C., Qin X., Boeckh M., Waghmare A. Characteristics and Outcomes of Coronavirus Infection in Children: The Role of Viral Factors and an Immunocompromised State. J. Pediatric Infect. Dis. Soc. 2019;8:21-28.

    Not in our library10.1093/jpids/pix093

  213. 213.

    Ogimi C., Greninger A.L., Waghmare A.A., Kuypers J.M., Shean R.C., Xie H., Leisenring W.M., Stevens-Ayers T.L., Jerome K.R., Englund J.A., et al. Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution. J. Infect. Dis. 2017;216:203-209.

    Not in our library10.1093/infdis/jix264

  214. 214.

    Ogimi C., Waghmare A.A., Kuypers J.M., Xie H., Yeung C.C., Leisenring W.M., Seo S., Choi S.M., Jerome K.R., Englund J.A., et al. Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and Patients with Hematologic Malignancies. Clin. Infect. Dis. 2017;64:1532-1539.

    Not in our library10.1093/cid/cix160

  215. 215.

    Guan Y., Zheng B.J., He Y.Q., Liu X.L., Zhuang Z.X., Cheung C.L., Luo S.W., Li P.H., Zhang L.J., Guan Y.J., et al. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science. 2003;302:276-278.

    Not in our library10.1126/science.1087139

  216. 216.
    Progress in Global Surveillance and Response Capacity 10 Years after Severe Acute Respiratory Syndrome · 2013
    Not checked
  217. 217.

    Cherry J.D. The chronology of the 2002-2003 SARS mini pandemic. Paediatr. Respir. Rev. 2004;5:262-269.

    Not in our library10.1016/j.prrv.2004.07.009

  218. 218.

    Cherry J.D., Krogstad P. SARS: The first pandemic of the 21st century. Pediatr. Res. 2004;56:1-5.

    Not in our library10.1203/01.pdr.0000129184.87042.fc

  219. 219.

    Van den Brand J.M., Haagmans B.L., van Riel D., Osterhaus A.D., Kuiken T. The Pathology and Pathogenesis of Experimental Severe Acute Respiratory Syndrome and Influenza in Animal Models. J. Comp. Pathol. 2014;151:83-112.

    Not in our library10.1016/j.jcpa.2014.01.004

  220. 220.

    Gu J., Gong E., Zhang B., Zheng J., Gao Z., Zhong Y., Zou W., Zhan J., Wang S., Xie Z., et al. Multiple organ infection and the pathogenesis of SARS. J. Exp. Med. 2005;202:415-424.

    Not in our library10.1084/jem.20050828

  221. 221.

    Raj V.S., Osterhaus A.D., Fouchier R.A., Haagmans B.L. MERS: Emergence of a novel human coronavirus. Curr. Opin. Virol. 2014;5:58-62.

    Not in our library10.1016/j.coviro.2014.01.010

  222. 222.
    Emergence of the Middle East respiratory syndrome coronavirus. · 2013
    Not checked
  223. 223.

    de Groot R.J., Baker S.C., Baric R.S., Brown C.S., Drosten C., Enjuanes L., Fouchier R.A., Galiano M., Gorbalenya A.E., Memish Z., et al. Middle East Respiratory Syndrome Coronavirus (MERS-CoV); Announcement of the Coronavirus Study Group. J. Virol. 2013;5:13-15.

    Not in our library10.1128/jvi.01244-13

  224. 224.

    Cotten M., Watson S.J., Kellam P., Al-Rabeeah A.A., Makhdoom H.Q., Assiri A., Al-Tawfiq J.A., Alhakeem R.F., Madani H., AlRabiah F.A., et al. Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: A descriptive genomic study. Lancet. 2013;382:1993-2002.

    Not in our library10.1016/s0140-6736(13)61887-5

  225. 225.

    Cotten M., Watson S.J., Zumla A.I., Makhdoom H.Q., Palser A.L., Ong S.H., Al Rabeeah A.A., Alhakeem R.F., Assiri A., Al-Tawfiq J.A., et al. Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus. mBio. 2014;5.

    Not in our library10.1128/mbio.01062-13

  226. 226.

    Memish Z.A., Cotten M., Watson S.J., Kellam P., Zumla A., Alhakeem R.F., Assiri A., Rabeeah A.A., Al-Tawfiq J.A. Community case clusters of Middle East respiratory syndrome coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: A descriptive genomic study. Int. J. Infect. Dis. 2014;23:63-68.

    Not in our library10.1016/j.ijid.2014.03.1372

  227. 227.

    Al-Tawfiq J.A., Assiri A., Memish Z.A. Middle East respiratory syndrome novel corona MERS-CoV infection. Epidemiology and outcome update. Saudi. Med. J. 2013;34:991-994.

    Not in our library

  228. 228.

    Assiri A., Al-Tawfiq J.A., Al-Rabeeah A.A., Al-Rabiah F.A., Al-Hajjar S., Al-Barrak A., Flemban H., Al-Nassir W.N., Balkhy H.H., Al-Hakeem R.F., et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: A descriptive study. Lancet Infect. Dis. 2013;13:752-761.

    Not in our library10.1016/s1473-3099(13)70204-4

  229. 229.

    Assiri A., McGeer A., Perl T.M., Price C.S., Al Rabeeah A.A., Cummings D.A., Alabdullatif Z.N., Assad M., Almulhim A., Makhdoom H., et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N. Engl. J. Med. 2013;369:407-416.

    Not in our library10.1056/nejmoa1306742

  230. 230.

    Haagmans B.L., Osterhaus A.D. Neutralizing the MERS coronavirus threat. Sci. Transl. Med. 2014;6:235fs19.

    Not in our library10.1126/scitranslmed.3009132

  231. 231.

    Cho S.Y., Kang J.M., Ha Y.E., Park G.E., Lee J.Y., Ko J.H., Lee J.Y., Kim J.M., Kang C.I., Jo I.J., et al. MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: An epidemiological outbreak study. Lancet. 2016;388:994-1001.

    Not in our library10.1016/s0140-6736(16)30623-7

  232. 232.

    Park H.Y., Lee E.J., Ryu Y.W., Kim Y., Kim H., Lee H., Yi S.J. Epidemiological investigation of MERS-CoV spread in a single hospital in South Korea, May to June 2015. Euro Surveill. 2015;20:1-6.

    Not in our library10.2807/1560-7917.es2015.20.25.21169

  233. 233.

    Hemida M.G. Middle East Respiratory Syndrome Coronavirus and the One Health concept. PeerJ. 2019;7:e7556.

    Not in our library10.7717/peerj.7556

  234. 234.

    Al-Omari A., Rabaan A.A., Salih S., Al-Tawfiq J.A., Memish Z.A. MERS coronavirus outbreak: Implications for emerging viral infections. Diagn. Microbiol. Infect. Dis. 2019;93:265-285.

    Not in our library10.1016/j.diagmicrobio.2018.10.011

  235. 235.

    Mackay I.M., Arden K.E. An Opportunistic Pathogen Afforded Ample Opportunities: Middle East Respiratory Syndrome Coronavirus. Viruses. 2017;9:369.

    Not in our library10.3390/v9120369

  236. 236.

    Hui D.S., Memish Z.A., Zumla A. Severe acute respiratory syndrome vs. the Middle East respiratory syndrome. Curr. Opin. Pulm. Med. 2014;20:233-241.

    Not in our library10.1097/mcp.0000000000000046

  237. 237.

    Peiris J.S., Guan Y., Yuen K.Y. Severe acute respiratory syndrome. Nat. Med. 2004;10:S88-S97.

    Not in our library10.1038/nm1143

  238. 238.

    Jevsnik M., Steyer A., Pokorn M., Mrvic T., Grosek S., Strle F., Lusa L., Petrovec M. The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study. PLoS ONE. 2016;11:e0155555.

    Not in our library10.1371/journal.pone.0155555

  239. 239.

    Riski H., Hovi T. Coronavirus infections of man associated with diseases other than the common cold. J. Med. Virol. 1980;6:259-265.

    Not in our library10.1002/jmv.1890060309

  240. 240.

    Gerna G., Passarani N., Battaglia M., Rondanelli E.G. Human enteric coronaviruses: Antigenic relatedness to human coronavirus OC43 and possible etiologic role in viral gastroenteritis. J. Infect. Dis. 1985;151:796-803.

    Not in our library10.1093/infdis/151.5.796

  241. 241.

    Resta S., Luby J.P., Rosenfeld C.R., Siegel J.D. Isolation and propagation of a human enteric coronavirus. Science. 1985;229:978-981.

    Not in our library10.1126/science.2992091

  242. 242.

    Esper F., Ou Z., Huang Y.T. Human coronaviruses are uncommon in patients with gastrointestinal illness. J. Clin. Virol. 2010;48:131-133.

    Not in our library10.1016/j.jcv.2010.03.007

  243. 243.

    Risku M., Lappalainen S., Rasanen S., Vesikari T. Detection of human coronaviruses in children with acute gastroenteritis. J. Clin. Virol. 2010;48:27-30.

    Not in our library10.1016/j.jcv.2010.02.013

  244. 244.

    Morfopoulou S., Brown J.R., Davies E.G., Anderson G., Virasami A., Qasim W., Chong W.K., Hubank M., Plagnol V., Desforges M., et al. Human Coronavirus OC43 Associated with Fatal Encephalitis. N. Engl. J. Med. 2016;375:497-498.

    Not in our library10.1056/nejmc1509458

  245. 245.

    Arbour N., Day R., Newcombe J., Talbot P.J. Neuroinvasion by human respiratory coronaviruses. J. Virol. 2000;74:8913-8921.

    Not in our library10.1128/jvi.74.19.8913-8921.2000

  246. 246.

    Cristallo A., Gambaro F., Biamonti G., Ferrante P., Battaglia M., Cereda P.M. Human coronavirus polyadenylated RNA sequences in cerebrospinal fluid from multiple sclerosis patients. New Microbiol. 1997;20:105-114.

    Not in our library

  247. 247.

    Fazzini E., Fleming J., Fahn S. Cerebrospinal fluid antibodies to coronavirus in patients with Parkinson’s disease. Mov. Disord. 1992;7:153-158.

    Not in our library10.1002/mds.870070210

  248. 248.

    Stewart J.N., Mounir S., Talbot P.J. Human coronavirus gene expression in the brains of multiple sclerosis patients. Virology. 1992;191:502-505.

    Not in our library10.1016/0042-6822(92)90220-j

  249. 249.

    Yeh E.A., Collins A., Cohen M.E., Duffner P.K., Faden H. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics. 2004;113:e73-e76.

    Not in our library10.1542/peds.113.1.e73

  250. 250.

    Chilvers M.A., McKean M., Rutman A., Myint B.S., Silverman M., O’Callaghan C. The effects of coronavirus on human nasal ciliated respiratory epithelium. Eur. Respir. J. 2001;18:965-970.

    Not in our library10.1183/09031936.01.00093001

  251. 251.

    Dijkman R., Jebbink M.F., Koekkoek S.M., Deijs M., Jonsdottir H.R., Molenkamp R., Ieven M., Goossens H., Thiel V., van der Hoek L. Isolation and characterization of current human coronavirus strains in primary human epithelial cell cultures reveal differences in target cell tropism. J. Virol. 2013;87:6081-6090.

    Not in our library10.1128/jvi.03368-12

  252. 252.

    Desforges M., Miletti T.C., Gagnon M., Talbot P.J. Activation of human monocytes after infection by human coronavirus 229E. Virus Res. 2007;130:228-240.

    Not in our library10.1016/j.virusres.2007.06.016

  253. 253.

    Collins A.R. In vitro detection of apoptosis in monocytes/macrophages infected with human coronavirus. Clin. Diagn Lab. Immunol. 2002;9:1392-1395.

    Not in our library10.1128/cdli.9.6.1392-1395.2002

  254. 254.

    Mesel-Lemoine M., Millet J., Vidalain P.O., Law H., Vabret A., Lorin V., Escriou N., Albert M.L., Nal B., Tangy F. A human coronavirus responsible for the common cold massively kills dendritic cells but not monocytes. J. Virol. 2012;86:7577-7587.

    Not in our library10.1128/jvi.00269-12

  255. 255.

    Wentworth D.E., Tresnan D.B., Turner B.C., Lerman I.R., Bullis B., Hemmila E.M., Levis R., Shapiro L.H., Holmes K.V. Cells of human aminopeptidase N (CD13) transgenic mice are infected by human coronavirus-229E in vitro, but not in vivo. Virology. 2005;335:185-197.

    Not in our library10.1016/j.virol.2005.02.023

  256. 256.

    Spiegel M., Weber F. Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus. Virol. J. 2006;3:17.

    Not in our library10.1186/1743-422x-3-17

  257. 257.

    Reuter J.D., Gomez D.L., Wilson J.H., Van Den Pol A.N. Systemic immune deficiency necessary for cytomegalovirus invasion of the mature brain. J. Virol. 2004;78:1473-1487.

    Not in our library10.1128/jvi.78.3.1473-1487.2004

  258. 258.

    Lassnig C., Sanchez C.M., Egerbacher M., Walter I., Majer S., Kolbe T., Pallares P., Enjuanes L., Muller M. Development of a transgenic mouse model susceptible to human coronavirus 229E. Proc. Natl. Acad. Sci. USA. 2005;102:8275-8280.

    Not in our library10.1073/pnas.0408589102

  259. 259.

    Mori I., Nishiyama Y., Yokochi T., Kimura Y. Olfactory transmission of neurotropic viruses. J. Neurovirology. 2005;11:129-137.

    Not in our library10.1080/13550280590922793

  260. 260.

    Durrant D.M., Ghosh S., Klein R.S. The Olfactory Bulb: An Immunosensory Effector Organ during Neurotropic Viral Infections. ACS Chem. Neurosci. 2016;7:464-469.

    Not in our library10.1021/acschemneuro.6b00043

  261. 261.

    Jacomy H., Talbot P.J. Vacuolating encephalitis in mice infected by human coronavirus OC43. Virology. 2003;315:20-33.

    Not in our library10.1016/s0042-6822(03)00323-4

  262. 262.

    McCray P.B., Pewe L., Wohlford-Lenane C., Hickey M., Manzel L., Shi L., Netland J., Jia H.P., Halabi C., Sigmund C.D., et al. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J. Virol. 2007;81:813-821.

    Not in our library10.1128/jvi.02012-06

  263. 263.

    Butler N., Pewe L., Trandem K., Perlman S. Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated. Virology. 2006;347:410-421.

    Not in our library10.1016/j.virol.2005.11.044

  264. 264.

    St-Jean J.R., Jacomy H., Desforges M., Vabret A., Freymuth F., Talbot P.J. Human respiratory coronavirus OC43: Genetic stability and neuroinvasion. J. Virol. 2004;78:8824-8834.

    Not in our library10.1128/jvi.78.16.8824-8834.2004

  265. 265.

    Netland J., Meyerholz D.K., Moore S., Cassell M., Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J. Virol. 2008;82:7264-7275.

    Not in our library10.1128/jvi.00737-08

  266. 266.

    Le Coupanec A., Desforges M., Meessen-Pinard M., Dube M., Day R., Seidah N.G., Talbot P.J. Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System. PLoS Pathog. 2015;11:e1005261.

    Not in our library10.1371/journal.ppat.1005261

  267. 267.

    Jacomy H., St-Jean J.R., Brison E., Marceau G., Desforges M., Talbot P.J. Mutations in the spike glycoprotein of human coronavirus OC43 modulate disease in BALB/c mice from encephalitis to flaccid paralysis and demyelination. J. Neurovirology. 2010;16:279-293.

    Not in our library10.3109/13550284.2010.497806

  268. 268.

    Brison E., Jacomy H., Desforges M., Talbot P.J. Glutamate excitotoxicity is involved in the induction of paralysis in mice after infection by a human coronavirus with a single point mutation in its spike protein. J. Virol. 2011;85:12464-12473.

    Not in our library10.1128/jvi.05576-11

  269. 269.

    Dube M., Le Coupanec A., Wong A.H.M., Rini J.M., Desforges M., Talbot P.J. Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43. J. Virol. 2018;92.

    Not in our library10.1128/jvi.00404-18

  270. 270.

    Xu J., Zhong S., Liu J., Li L., Li Y., Wu X., Li Z., Deng P., Zhang J., Zhong N., et al. Detection of severe acute respiratory syndrome coronavirus in the brain: Potential role of the chemokine mig in pathogenesis. Clin. Infect. Dis. 2005;41:1089-1096.

    Not in our library10.1086/444461

  271. 271.

    Turgay C., Emine T., Ozlem K., Muhammet S.P., Haydar A.T. A rare cause of acute flaccid paralysis: Human coronaviruses. J. Pediatr. Neurosci. 2015;10:280-281.

    Not in our library10.4103/1817-1745.165716

  272. 272.
    Possible Central Nervous System Infection by SARS Coronavirus · 2004
    No notice
  273. 273.
    Guillain–Barré syndrome with unilateral peripheral facial and bulbar palsy in a child: A case report · 2019
    Not checked
  274. 274.

    Principi N., Bosis S., Esposito S. Effects of coronavirus infections in children. Emerg. Infect. Dis. 2010;16:183-188.

    Not in our library10.3201/eid1602.090469

  275. 275.

    Tsai L.K., Hsieh S.T., Chang Y.C. Neurological manifestations in severe acute respiratory syndrome. Acta Neurol. Taiwan. 2005;14:113-119.

    Not in our library

  276. 276.
    Neurological Complications of Middle East Respiratory Syndrome Coronavirus: A Report of Two Cases and Review of the Literature · 2016
    No notice
  277. 277.
    Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV) · 2015
    No notice
  278. 278.

    Kim K.H., Tandi T.E., Choi J.W., Moon J.M., Kim M.S. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: Epidemiology, characteristics and public health implications. J. Hosp. Infect. 2017;95:207-213.

    Not in our library10.1016/j.jhin.2016.10.008

  279. 279.

    Li Y., Li H., Fan R., Wen B., Zhang J., Cao X., Wang C., Song Z., Li S., Li X., et al. Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children. Intervirology. 2016;59:163-169.

    Not in our library10.1159/000453066

  280. 280.

    Murray R.S., Brown B., Brian D., Cabirac G.F. Detection of coronavirus RNA and antigen in multiple sclerosis brain. Ann. Neurol. 1992;31:525-533.

    Not in our library10.1002/ana.410310511

  281. 281.

    Sibley W.A., Bamford C.R., Clark K. Clinical viral infections and multiple sclerosis. Lancet. 1985;1:1313-1315.

    Not in our library10.1016/s0140-6736(85)92801-6

  282. 282.

    Johnson-Lussenburg C.M., Zheng Q. Coronavirus and multiple sclerosis: Results of a case/control longitudinal serological study. Adv. Exp. Med. Biol. 1987;218:421-429.

    Not in our library10.1007/978-1-4684-1280-2_51

  283. 283.

    Fehr A.R., Perlman S. Coronaviruses: An overview of their replication and pathogenesis. Methods Mol. Biol. 2015;1282:1-23.

    Not in our library10.1007/978-1-4939-2438-7_1

  284. 284.

    Tseng S.S. SARS, avian flu, bioterror: Infection control awareness for the optometrist. Clin. Exp. Optom. 2007;90:31-35.

    Not in our library10.1111/j.1444-0938.2006.00086.x

  285. 285.

    Severance E.G., Dickerson F.B., Viscidi R.P., Bossis I., Stallings C.R., Origoni A.E., Sullens A., Yolken R.H. Coronavirus immunoreactivity in individuals with a recent onset of psychotic symptoms. Schizophr. Bull. 2011;37:101-107.

    Not in our library10.1093/schbul/sbp052

  286. 286.

    Jean A., Quach C., Yung A., Semret M. Severity and outcome associated with human coronavirus OC43 infections among children. Pediatr. Infect. Dis. J. 2013;32:325-329.

    Not in our library10.1097/inf.0b013e3182812787

  287. 287.

    Jacomy H., Fragoso G., Almazan G., Mushynski W.E., Talbot P.J. Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice. Virology. 2006;349:335-346.

    Not in our library10.1016/j.virol.2006.01.049

  288. 288.

    Do Carmo S., Jacomy H., Talbot P.J., Rassart E. Neuroprotective effect of apolipoprotein D against human coronavirus OC43-induced encephalitis in mice. J. Neurosci. 2008;28:10330-10338.

    Not in our library10.1523/jneurosci.2644-08.2008

  289. 289.

    Brison E., Jacomy H., Desforges M., Talbot P.J. Novel treatment with neuroprotective and antiviral properties against a neuroinvasive human respiratory virus. J. Virol. 2014;88:1548-1563.

    Not in our library10.1128/jvi.02972-13

  290. 290.

    Kim J.E., Heo J.H., Kim H.O., Song S.H., Park S.S., Park T.H., Ahn J.Y., Kim M.K., Choi J.P. Neurological Complications during Treatment of Middle East Respiratory Syndrome. J. Clin. Neurol. 2017;13:227-233.

    Not in our library10.3988/jcn.2017.13.3.227

  291. 291.

    Tomishima M.J., Enquist L.W. In vivo egress of an alphaherpesvirus from axons. J. Virol. 2002;76:8310-8317.

    Not in our library10.1128/jvi.76.16.8310-8317.2002

  292. 292.

    Shen L., Yang Y., Ye F., Liu G., Desforges M., Talbot P.J., Tan W. Safe and Sensitive Antiviral Screening Platform Based on Recombinant Human Coronavirus OC43 Expressing the Luciferase Reporter Gene. Antimicrob. Agents Chemother. 2016;60:5492-5503.

    Not in our library10.1128/aac.00814-16

  293. 293.

    Shen L., Niu J., Wang C., Huang B., Wang W., Zhu N., Deng Y., Wang H., Ye F., Cen S., et al. High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses. J. Virol. 2019;93.

    Not in our library10.1128/jvi.00023-19

  294. 294.

    Niu J., Shen L., Huang B., Ye F., Zhao L., Wang H., Deng Y., Tan W. Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice. Antivir. Res. 2020;173:104646.

    Not in our library10.1016/j.antiviral.2019.104646

  295. 295.

    Desforges M., Desjardins J., Zhang C., Talbot P.J. The acetyl-esterase activity of the hemagglutinin-esterase protein of human coronavirus OC43 strongly enhances the production of infectious virus. J. Virol. 2013;87:3097-3107.

    Not in our library10.1128/jvi.02699-12

  296. 296.

    Stodola J.K., Dubois G., Le Coupanec A., Desforges M., Talbot P.J. The OC43 human coronavirus envelope protein is critical for infectious virus production and propagation in neuronal cells and is a determinant of neurovirulence and CNS pathology. Virology. 2018;515:134-149.

    Not in our library10.1016/j.virol.2017.12.023

  297. 297.

    Arbour N., Cote G., Lachance C., Tardieu M., Cashman N.R., Talbot P.J. Acute and persistent infection of human neural cell lines by human coronavirus OC43. J. Virol. 1999;73:3338-3350.

    Not in our library10.1128/jvi.73.4.3338-3350.1999

  298. 298.

    Arbour N., Ekande S., Cote G., Lachance C., Chagnon F., Tardieu M., Cashman N.R., Talbot P.J. Persistent infection of human oligodendrocytic and neuroglial cell lines by human coronavirus 229E. J. Virol. 1999;73:3326-3337.

    Not in our library10.1128/jvi.73.4.3326-3337.1999

  299. 299.

    Vasek M.J., Garber C., Dorsey D., Durrant D.M., Bollman B., Soung A., Yu J., Perez-Torres C., Frouin A., Wilton D.K., et al. A complement-microglial axis drives synapse loss during virus-induced memory impairment. Nature. 2016;534:538-543.

    Not in our library10.1038/nature18283

  300. 300.

    Agner S.C., Klein R.S. Viruses have multiple paths to central nervous system pathology. Curr. Opin. Neurol. 2018;31:313-317.

    Not in our library10.1097/wco.0000000000000556

  301. 301.

    Kurtzke J.F. Epidemiologic evidence for multiple sclerosis as an infection. Clin. Microbiol. Rev. 1993;6:382-427.

    Not in our library10.1128/cmr.6.4.382

  302. 302.

    Cusick M.F., Libbey J.E., Fujinami R.S. Multiple sclerosis: Autoimmunity and viruses. Curr. Opin. Rheumato. 2013;25:496-501.

    Not in our library10.1097/bor.0b013e328362004d

  303. 303.

    Gilden D.H. Infectious causes of multiple sclerosis. Lancet Neurol. 2005;4:195-202.

    Not in our library10.1016/s1474-4422(05)70023-5

  304. 304.

    Kakalacheva K., Munz C., Lunemann J.D. Viral triggers of multiple sclerosis. Biochim. Biophys Acta. 2011;1812:132-140.

    Not in our library10.1016/j.bbadis.2010.06.012

  305. 305.

    Saberi A., Akhondzadeh S., Kazemi S. Infectious agents and different course of multiple sclerosis: A systematic review. Acta Neurol. Belg. 2018;118:361-377.

    Not in our library10.1007/s13760-018-0976-y

  306. 306.
    Viruses and Autoimmunity: A Review on the Potential Interaction and Molecular Mechanisms · 2019
    No notice
  307. 307.

    Desforges M., Favreau D.J., Brison E., Desjardins J., Meessen-Pinard M., Jacomy H., Talbot P.J., Singh S.K., Ruzek D. Human Coronaviruses. Respiratory Pathogens Revisited as Infectious Neuroinvasive, Neurtropic, and Neurovirulent Agents. Neuroviral Infections. RNA Viruses and Retroviruses. 2013;93-121.

    Not in our library

  308. 308.

    Boucher A., Desforges M., Duquette P., Talbot P.J. Long-term human coronavirus-myelin cross-reactive T-cell clones derived from multiple sclerosis patients. Clin. Immunol. 2007;123:258-267.

    Not in our library10.1016/j.clim.2007.02.002

  309. 309.

    Talbot P.J., Paquette J.S., Ciurli C., Antel J.P., Ouellet F. Myelin basic protein and human coronavirus 229E cross-reactive T cells in multiple sclerosis. Ann. Neurol. 1996;39:233-240.

    Not in our library10.1002/ana.410390213

  310. 310.

    Amor S., Puentes F., Baker D., van der Valk P. Inflammation in neurodegenerative diseases. Immunology. 2010;129:154-169.

    Not in our library10.1111/j.1365-2567.2009.03225.x

  311. 311.

    Carmen J., Rothstein J.D., Kerr D.A. Tumor necrosis factor-alpha modulates glutamate transport in the CNS and is a critical determinant of outcome from viral encephalomyelitis. Brain Res. 2009;1263:143-154.

    Not in our library10.1016/j.brainres.2009.01.040

  312. 312.

    Favreau D.J., Desforges M., St-Jean J.R., Talbot P.J. A human coronavirus OC43 variant harboring persistence-associated mutations in the S glycoprotein differentially induces the unfolded protein response in human neurons as compared to wild-type virus. Virology. 2009;395:255-267.

    Not in our library10.1016/j.virol.2009.09.026

  313. 313.

    Favreau D.J., Meessen-Pinard M., Desforges M., Talbot P.J. Human coronavirus-induced neuronal programmed cell death is cyclophilin d dependent and potentially caspase dispensable. J. Virol. 2012;86:81-93.

    Not in our library10.1128/jvi.06062-11

  314. 314.

    Meessen-Pinard M., Le Coupanec A., Desforges M., Talbot P.J. Pivotal Role of Receptor-Interacting Protein Kinase 1 and Mixed Lineage Kinase Domain-Like in Neuronal Cell Death Induced by the Human Neuroinvasive Coronavirus OC43. J. Virol. 2017;91.

    Not in our library10.1128/jvi.01513-16

  315. 315.

    Galluzzi L., Vitale I., Abrams J.M., Alnemri E.S., Baehrecke E.H., Blagosklonny M.V., Dawson T.M., Dawson V.L., El-Deiry W.S., Fulda S., et al. Molecular definitions of cell death subroutines: Recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ. 2012;19:107-120.

    Not in our library10.1038/cdd.2011.96

  316. 316.
    Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence · 2011
    No notice
  317. 317.

    Zhao L., Birdwell L.D., Wu A., Elliott R., Rose K.M., Phillips J.M., Li Y., Grinspan J., Silverman R.H., Weiss S.R. Cell-type-specific activation of the oligoadenylate synthetase-RNase L pathway by a murine coronavirus. J. Virol. 2013;87:8408-8418.

    Not in our library10.1128/jvi.00769-13

  318. 318.

    Zhao L., Jha B.K., Wu A., Elliott R., Ziebuhr J., Gorbalenya A.E., Silverman R.H., Weiss S.R. Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology. Cell Host Microbe. 2012;11:607-616.

    Not in our library10.1016/j.chom.2012.04.011

  319. 319.

    Zhao L., Rose K.M., Elliott R., Van Rooijen N., Weiss S.R. Cell-type-specific type I interferon antagonism influences organ tropism of murine coronavirus. J. Virol. 2011;85:10058-10068.

    Not in our library10.1128/jvi.05075-11

  320. 320.

    Talbot P.J., Desforges M., Brison E., Jacomy H., Tkachev S. Coronaviruses as Encephalitis-inducing infectious agents. Non-Flavirus Encephalitis. 2011;185-202.

    Not in our library

  321. 321.

    Wilson M.R., Sample H.A., Zorn K.C., Arevalo S., Yu G., Neuhaus J., Federman S., Stryke D., Briggs B., Langelier C., et al. Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis. N. Engl. J. Med. 2019;380:2327-2340.

    Not in our library10.1056/nejmoa1803396

  322. 322.

    Souza L.D.C., Blawid R., Silva J.M.F., Nagata T. Human virome in nasopharynx and tracheal secretion samples. Mem. Inst. Oswaldo Cruz. 2019;114:e190198.

    Not in our library10.1590/0074-02760190198

  323. 323.

    Koch R. The Aetiology of Tuberculosis (Translation of Die Aetiologie der Tuberculose (1882). 1942.

    Not in our library

  324. 324.

    Fredericks D.N., Relman D.A. Sequence-based identification of microbial pathogens: A reconsideration of Koch’s postulates. Clin. Microbiol. Rev. 1996;9:18-33.

    Not in our library10.1128/cmr.9.1.18

  325. 325.

    Hill A.B. The Environment and Disease: Association or Causation? Proc. R. Soc. Med. 1965;58:295-300.

    Not in our library10.1177/003591576505800503

  326. 326.

    Giovannoni G., Cutter G.R., Lunemann J., Martin R., Munz C., Sriram S., Steiner I., Hammerschlag M.R., Gaydos C.A. Infectious causes of multiple sclerosis. Lancet Neurol. 2006;5:887-894.

    Not in our library10.1016/s1474-4422(06)70577-4

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