Mutations Associated with Viral Sequences Isolated from Mice Persistently Infected with MHV-JHM

Fleming, John O.; Adami, Cecilia; Pooley, Joan C.; Glomb, Juliet; Stecker, Eric; Fazal, Fabeha; Baker, Susan C.

doi:10.1007/978-1-4615-1899-0_94

Cited by 13 publications

(12 citation statements)

References 6 publications

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“…Evolution of coronavirus during persistent infection has been investigated using murine coronaviruses, both in vitro and in vivo Fleming et al, 1993Fleming et al, , 1995Rowe et al, 1997aRowe et al, , 1997bRowe et al, , 1998Steinhauer et al, 1992). Murine coronaviruses comprise several pathogenic strains historically known as mouse hepatitis virus (MHV), although only a few are primarily hepatotropic (Haring and Perlman, 2001;Navas-Martín and Weiss, 2003).…”

Section: Coronavirus Evolutionmentioning

confidence: 99%

Coronavirus replication and pathogenesis: Implications for the recent outbreak of severe acute respiratory syndrome (SARS), and the challenge for vaccine development

Navas-Martín

Weiss

2004

J Neurovirol

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Section: Coronavirus Evolutionmentioning

confidence: 99%

Coronavirus replication and pathogenesis: Implications for the recent outbreak of severe acute respiratory syndrome (SARS), and the challenge for vaccine development

Navas-Martín

Weiss

2004

J Neurovirol

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“…Antibody responses are crucial in controlling spread of virus (Ramakrishna et al, 2002). Persistence of viral RNA and protein has been observed, mostly in glial cells including oligodendrocytes, for up to a year post infection (Knobler et al, 1982;Lavi et al, 1984;Perlman and Ries, 1987;Adami et al, 1995;Parra et al, 1999;Fleming et al, 1995). Analysis of virus RNA during persistence indicates that many viral genomes have mutations, particularly point and deletion mutations in the S and N genes (Adami et al, 1995).…”

Section: Mouse Hepatitis Virus (Mhv)mentioning

confidence: 99%

“…Adami C, Pooley J, Glomb J, Stecker E, Fazal F, Fleming JO, Baker SC (1995). Evolution of mouse hepatitis virus (MHV) during chronic infection: quasispecies nature of the persisting MHV RNA.…”

Section: Referencesmentioning

confidence: 99%

Virus Demyelination

Fazakerley

Walker

2003

J Neurovirol

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A number of viruses can initiate central nervous system (CNS) diseases that include demyelination as a major feature of neuropathology. In humans, the most prominent demyelinating diseases are progressive multifocal leukoencephalopathy, caused by JC papovirus destruction of oligodendrocytes, and subacute sclerosing panencephalitis, an invariably fatal childhood disease caused by persistent measles virus. The most common neurological disease of young adults in the developed world, multiple sclerosis, is also characterized by lesions of inflammatory demyelination; however, the etiology of this disease remains an enigma. A viral etiology is possible, because most demyelinating diseases of known etiology in both man and animals are viral. Understanding of the pathogenesis of virus-induced demyelination derives for the most part from the study of animal models. Studies with neurotropic strains of mouse hepatitis virus, Theiler's virus, and Semliki Forest virus have been at the forefront of this research. These models demonstrate how viruses enter the brain, spread, persist, and interact with immune responses. Common features are an ability to infect and persist in glial cells, generation of predominantly CD8(+) responses, which control and clear the early phase of virus replication but which fail to eradicate the infection, and lesions of inflammatory demyelination. In most cases demyelination is to a limited extent the result of direct virus destruction of oligodendrocytes, but for the most part is the consequence of immune and inflammatory responses. These models illustrate the roles of age and genetic susceptibility and establish the concept that persistent CNS infection can lead to the generation of CNS autoimmune responses.

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“…The immune response clears infectious virus within 2 wk, but fails to achieve sterile immunity. Viral RNA, and in some cases Ag, can be detected for up to 2 yr and is associated with ongoing primary CNS demyelination (8).…”

mentioning

confidence: 99%

Contributions of CD8+ T Cells and Viral Spread to Demyelinating Disease

Marten

Stohlman

Atkinson

et al. 2000

The Journal of Immunology

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Acute and chronic demyelination are hallmarks of CNS infection by the neurotropic JHM strain of mouse hepatitis virus. Although infectious virus is cleared by CD8+ T cells, both viral RNA and activated CD8+ T cells remain in the CNS during persistence potentially contributing to pathology. To dissociate immune from virus-mediated determinants initiating and maintaining demyelinating disease, mice were infected with two attenuated viral variants differing in a hypervariable region of the spike protein. Despite similar viral replication and tropism, one infection was marked by extensive demyelination and paralysis, whereas the other resulted in no clinical symptoms and minimal neuropathology. Mononuclear cells from either infected brain exhibited virus specific ex vivo cytolytic activity, which was rapidly lost during viral clearance. As revealed by class I tetramer technology the paralytic variant was superior in inducing specific CD8+ T cells during the acute disease. However, after infectious virus was cleared, twice as many virus-specific IFN-γ-secreting CD8+ T cells were recovered from the brains of asymptomatic mice compared with mice undergoing demyelination, suggesting that IFN-γ ameliorates rather than perpetuates JHM strain of mouse hepatitis virus-induced demyelination. The present data thus indicate that in immunocompetent mice, effector CD8+ T cells control infection without mediating either clinical disease or demyelination. In contrast, demyelination correlated with early and sustained infection of the spinal cord. Rapid viral spread, attributed to determinants within the spike protein and possibly perpetuated by suboptimal CD8+ T cell effector function, thus ultimately leads to the process of immune-mediated demyelination.

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Mutations Associated with Viral Sequences Isolated from Mice Persistently Infected with MHV-JHM

Cited by 13 publications

References 6 publications

Coronavirus replication and pathogenesis: Implications for the recent outbreak of severe acute respiratory syndrome (SARS), and the challenge for vaccine development

Coronavirus replication and pathogenesis: Implications for the recent outbreak of severe acute respiratory syndrome (SARS), and the challenge for vaccine development

Virus Demyelination

Contributions of CD8+ T Cells and Viral Spread to Demyelinating Disease

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