Persistence of Viral RNA in the Central Nervous System of Mice Inoculated with MHV-4

Fleming, John O.; Houtman, J. J.; Alaca, Hulya; Hinze, Harry C.; McKenzie, Debbie; Aiken, Judd M.; Bleasdale, Thomas; Baker, Susan C.

doi:10.1007/978-1-4615-2996-5_50

Cited by 26 publications

(24 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we verified the presence of HCoV RNA within a large panel of human brain autopsy samples. We looked for viral RNA and not viral protein or infectious virions since it has been established that during persistent MHV infections of murine CNS, viral proteins and virions could not be detected for periods as long as could viral RNA (22). Coded brain samples were treated blindly, and only when experiments were completed were the codes broken to ensure complete objectivity in the interpretation of results.…”

Section: Resultsmentioning

confidence: 99%

Neuroinvasion by Human Respiratory Coronaviruses

Arbour

Day

Newcombe

et al. 2000

J Virol

472

482

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by patches of demyelination and infiltration of inflammatory cells (21). The etiology of this disabling diseasehas not yet been determined, but both genetic factors, such as genes encoding human leukocyte antigens, T-cell receptors, and myelin basic protein (MBP) (18,19,26), and environmental factors such as viruses have been implicated (31). At least four human demyelinating diseases have a known viral etiology: subacute sclerosing panencephalitis as a late complication of measles virus infection of childhood (35), progressive multifocal leukoencephalopathy caused by the JC papovavirus (57), encephalopathy and myelopathy (neuro-AIDS) caused by human immunodeficiency virus (43), and human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (28). Over the last decades, several viruses have been associated with MS, based on detection of virions, viral nucleic acids, or viral proteins in CNS or the presence of antiviral antibodies in serum and/or cerebrospinal fluid. A confirmed association with MS is awaited but may involve more than one virus.Several studies have associated human coronaviruses (HCoV) with MS. Coronavirus-like particles were detected in autopsied brain tissue from an MS patient (56). Two coronaviruses that are molecularly related to murine neurotropic coronaviruses were isolated from brain material obtained at autopsy from two MS patients (9). Intrathecal anti-HCoV antibody synthesis indicative of a CNS infection was reported in MS patients (45). HCoV RNA was detected in MS patient brains (37, 51) and in cerebrospinal fluid of MS and other neurological disease (OND) patients (15). Coronavirus antigens were also detected in MS patient brains (37). Moreover, we have shown that HCoV can infect human astrocytes and microglia in primary cultures (8) and can acutely and persistently infect immortalized human glial cells (4, 5). Thus, accumulating evidence suggests that these viruses, first isolated as pathogens of the respiratory tract and now associated with up to one-third of human common colds (39), might be neurotropic, neuroinvasive, and neurovirulent in humans, as is the case for their murine counterpart, the coronavirus mouse hepatitis virus (MHV). Interestingly, upper respiratory infections of viral origin were shown to be an important trigger of MS attacks (2,40,48). Moreover, coronavirus seasonal patterns fit the observed occurrence of MS exacerbations (48).MHV-induced demyelinating disease involving coronaviruses is used as an animal model for elucidating the complex pathogenesis of MS. As for MS, MHV pathogenesis is multifactorial (27). Its outcome is influenced by genetics of the host and virus, dose and route of inoculation, and host age and immunological status at the time of infection (58). Neurotropic MHV strains could invade the CNS following an intranasal inoculation in mice (34) and could also gain access to the CNS via the hematogenous and/or lymphatic systems in mice (7) and i...

show abstract

Section: Resultsmentioning

confidence: 99%

Neuroinvasion by Human Respiratory Coronaviruses

Arbour

Day

Newcombe

et al. 2000

J Virol

472

482

View full text Add to dashboard Cite

show abstract

“…Furthermore, large numbers of virus-specific CD8 ϩ T cells are found within the CNS for several weeks following clearance of both infectious viruses (5,21). Nevertheless, V-1-infected mice fail to achieve sterile immunity, resulting in a persistent infection as evidenced by the detection of life-long persisting vRNA (4,12). Persistence is primarily localized to the spinal cord white matter and is associated with ongoing focal demyelination and chronic mononuclear cell infiltration, hallmarks reminiscent of the human disease multiple sclerosis.…”

Section: Cd8mentioning

confidence: 99%

“…(4,12). Although V-2 infection is clinically asymptomatic, the ability of V-2 to persist is unknown.…”

Section: Jhmv Variant V-1 Persistently Infects the Spinal Cord Wherementioning

confidence: 99%

“…Although V-1 and V-2 initially replicate in the brain, V-1 Ag and RNA are most abundant in the spinal cords in persistently infected mice (4,12,21). To verify complete clearance of V-2 RNA from the CNS while confirming the ability of V-1 to establish persistence within the spinal cord, the presence of vRNA in spinal cords from infected and naive mice was tested ( was readily detectable in all mice to day 11 p.i.…”

Section: Jhmv Variant V-1 Persistently Infects the Spinal Cord Wherementioning

confidence: 99%

See 1 more Smart Citation

Role of Viral Persistence in Retaining CD8⁺T Cells within the Central Nervous System

Marten¹,

Stohlman

Bergmann

2000

J Virol

124

View full text Add to dashboard Cite

The continued presence of virus-specific CD8؉ T cells within the central nervous system (CNS) following resolution of acute viral encephalomyelitis implicates organ-specific retention. The role of viral persistence in locally maintaining T cells was investigated by infecting mice with either a demyelinating, paralytic (V-1) or nonpathogenic (V-2) variant of a neurotropic mouse hepatitis virus, which differ in the ability to persist within the CNS. Class I tetramer technology revealed more infiltrating virus-specific CD8 ؉ T cells during acute V-1 compared to V-2 infection. However, both total and virus-specific CD8 ؉ T cells accumulated at similar peak levels in spinal cords by day 10 postinfection (p.i.). Decreasing viral RNA levels in both brains and spinal cords following initial virus clearance coincided with an overall progressive loss of both total and virus-specific CD8

show abstract

“…Each cell type employs unique effector mechanisms to clear infectious virus from oligodendrocytes, astrocytes and microglia [8]. Following viral clearance, viral RNA persists, resulting in a chronic demyelinating disease that is both clinically and histologically similar to the human demyelinating disease multiple sclerosis (MS) [9][10][11][12][13]. Numerous studies support the notion that immunopathologic responses to viral antigens expressed in infected tissues are the primary mechanisms contributing to MHVinduced demyelination [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Differential roles for CXCR3 in CD4⁺ and CD8⁺ T cell trafficking following viral infection of the CNS

et al. 2006

View full text Add to dashboard Cite

Lymphocyte infiltration into the central nervous system (CNS) following viral infection represents an important component of host defense and is required for control of viral replication. However, the mechanisms governing inflammation in response to viral infection of the CNS are not well understood. Following intracranial (i.c.) infection of susceptible mice with mouse hepatitis virus (MHV), mice develop an acute encephalomyelitis followed by a chronic demyelinating disease. The CXC chemokine ligand 10 (CXCL10) is expressed following MHV infection and signals T cells to migrate into the CNS. The functional contribution of the CXCL10 receptor CXCR3 in host defense and disease in response to MHV infection was evaluated. The majority of CD4 + and CD8 + T cells infiltrating the CNS following MHV infection express CXCR3. Administration of anti-CXCR3 antibody reduced CD4 + T cell infiltration (p 0.05), while CD8 + T cell trafficking was not affected. Anti-CXCR3 treatment during chronic disease correlated with improved motor skills and reduced demyelination. The selective effect of anti-CXCR3 treatment on CD4 + T cells was not the result of either reduced proliferation or modulation in chemokine receptor gene expression. Therefore, CXCR3 signaling has a non-redundant role in T cell subset trafficking in response to viral infection.

show abstract

Persistence of Viral RNA in the Central Nervous System of Mice Inoculated with MHV-4

Cited by 26 publications

References 12 publications

Neuroinvasion by Human Respiratory Coronaviruses

Neuroinvasion by Human Respiratory Coronaviruses

Role of Viral Persistence in Retaining CD8⁺T Cells within the Central Nervous System

Differential roles for CXCR3 in CD4⁺ and CD8⁺ T cell trafficking following viral infection of the CNS

Contact Info

Product

Resources

About

Persistence of Viral RNA in the Central Nervous System of Mice Inoculated with MHV-4

Cited by 26 publications

References 12 publications

Neuroinvasion by Human Respiratory Coronaviruses

Neuroinvasion by Human Respiratory Coronaviruses

Role of Viral Persistence in Retaining CD8+T Cells within the Central Nervous System

Differential roles for CXCR3 in CD4+ and CD8+ T cell trafficking following viral infection of the CNS

Contact Info

Product

Resources

About

Role of Viral Persistence in Retaining CD8⁺T Cells within the Central Nervous System

Differential roles for CXCR3 in CD4⁺ and CD8⁺ T cell trafficking following viral infection of the CNS