A Murine Virus (Jhm) Causing Disseminated Encephalomyelitis With Extensive Destruction of Myelin

Cheever, F. S.; Daniels, Jerry C.; Pappenheimer, Alwin M.; Bailey, Orville T.

doi:10.1084/jem.90.3.181

Cited by 295 publications

(186 citation statements)

References 2 publications

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“…The different forms of encephalomyelitis induced by murine coronaviruses (MHV) in rodents have received much attention as a model for investigating possible mechanisms of virus-induced demyelination and multiple sclerosis in humans. The neurotropic strain JHM (MHV-JHM) causes acute and chronic demyelinating diseases in mice and rats (Cheever et al, 1949;Nagashima et al 1978Nagashima et al , 1979Sorensen et al, 1980;Stohlman & Weiner, 1981;Wege et al, 1984b;Kyuwa & Stohlman, 1990). Apart from host factors such as age and genetic background, biological properties of the virus variant also determine the outcome of infection.…”

Section: Introductionmentioning

confidence: 99%

An immunodominant CD4+ T cell site on the nucleocapsid protein of murine coronavirus contributes to protection against encephalomyelitis

Schliephake¹,

Korner²,

Flory³

et al. 1993

Journal of General Virology

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The murine coronavirus neurotropic strain JHM (MHV-JHM) nucleocapsid CN) protein induces a strong Thelper cell response in Lewis rats. It has been shown previously that N-specific CD4 ÷ T cells can confer protection against acute disease upon transfer to otherwise lethally infected rats. To define the major antigenic regions that elicit this T cell response, truncated fragments of N protein were expressed from a bacterial expression vector and employed as T cell antigens. Lymphocytes from either MHV-JHM-infected or immunized rats were stimulated in culture with virus antigen, grown and tested for their specificity to the N protein fragments. The carboxy-terminally located C4-N fragment (95 amino acids) induced the most pronounced proliferative response irrespective of whether the lymphocyte culture was derived from immunized or MHV-JHM-infected rats. We established T cell lines specific for the truncated N protein fragments and tested their potential to mediate protection by transfer experiments. Only the T cell line C4-N and the T cell line specific for the full-length N protein were protective. By contrast, all truncated N protein fragments elicited a humoral immune response and contained antigenic sites recognized by antibodies from diseased rats.

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Section: Introductionmentioning

confidence: 99%

An immunodominant CD4+ T cell site on the nucleocapsid protein of murine coronavirus contributes to protection against encephalomyelitis

Schliephake¹,

Korner²,

Flory³

et al. 1993

Journal of General Virology

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“…Cheerer et al (1949) first described a delayed encephalomyelitis associated with demyelination in rats infected with the coronavirus JHM. These early observations have recently been expanded, and infection of rats and mice with JHM virus has become a model for the study of demyelinating diseases (Nagashima et al, 1978(Nagashima et al, , 1979(Nagashima et al, , S6rensen et al, 1980Stohlman & Weiner, 1981 ;Knobler et al, 1982;Watanabe el al., 1983).…”

Section: Introductionmentioning

confidence: 99%

Adaptation of Coronavirus JHM to Persistent Infection of Murine Sac(-) Cells

Baybutt

Wege

Carter

et al. 1984

Journal of General Virology

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SUMMARYCoronaviruses can establish persistent infections in the central nervous system of rodents, and these are associated with demyelinating encephalomyelitis. The effects of persistence on the virus are difficult to study in vivo but may have a crucial influence on the course of infection. We therefore produced a persistent infection in vitro using the neurotropic coronavirus JHM, in order to investigate the events underlying the establishment of such an infection and the adaptation of the virus to persistence. The persistent infection was maintained for over 115 passages and continued to release high levels of infectious virus. During the 18 months of culture the number of cells expressing virus antigen detected by indirect immune fluorescence decreased to 40 ~. Analysis showed that the carried virus contained a significant proportion of heterogeneous temperature-sensitive mutants. All virus clones isolated possessed the capacity to induce a more productive growth cycle, a less pronounced cytopathic effect and showed a much reduced neurovirulence when inoculated into newborn and weanling rats. Evidence for structural changes involving the surface peplomer protein (E2) was obtained using hybridoma antibodies, which neutralized the parental JHM virus but not the JHM-Pi virus. Defective interfering particles and interferon activities have been excluded as possible agents instrumental in the establishment and maintenance of the chronic infection, and we suggest that the emergence of virus variants of lowered virulence is central to these processes.

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“…nstillation of a murine coronavirus, such as mouse hepatitis virus (MHV) 4 (a positive-strand RNA virus), into the CNS of C57BL/6 mice results in rapid growth and spread within the parenchyma with astrocytes, microglia, and oligodendrocytes being primary targets for replication (1)(2)(3)(4)(5). In response to MHV infection, T cells rapidly infiltrate into the CNS and reduce virus burden by cytolytic activity and IFN-␥ secretion (6,7).…”

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confidence: 99%

Expression of CXC Chemokine Ligand 10 from the Mouse Hepatitis Virus Genome Results in Protection from Viral-Induced Neurological and Liver Disease

Walsh

Edwards

Romero

et al. 2007

The Journal of Immunology

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Using the recombinant murine coronavirus mouse hepatitis virus (MHV) expressing the T cell-chemoattractant CXCL10 (MHV-CXCL10), we demonstrate a potent antiviral role for CXCL10 in host defense. Instillation of MHV-CXCL10 into the CNS of CXCL10-deficient (CXCL10−/−) mice resulted in viral infection and replication in both brain and liver. Expression of virally encoded CXCL10 within the brain protected mice from death and correlated with increased infiltration of T lymphocytes, enhanced IFN-γ secretion, and accelerated viral clearance when compared with mice infected with an isogenic control virus, MHV. Similarly, viral clearance from the livers of MHV-CXCL10-infected mice was accelerated in comparison to MHV-infected mice, yet was independent of enhanced infiltration of T lymphocytes and NK cells. Moreover, CXCL10−/− mice infected with MHV-CXCL10 were protected from severe hepatitis as evidenced by reduced pathology and serum alanine aminotransferase levels compared with MHV-infected mice. CXCL10-mediated protection within the liver was not dependent on CXC-chemokine receptor 2 (CXCR2) signaling as anti-CXCR2 treatment of MHV-CXCL10-infected mice did not modulate viral clearance or liver pathology. In contrast, treatment of MHV-CXCL10-infected CXCL10−/− mice with anti-CXCL10 Ab resulted in increased clinical disease correlating with enhanced viral recovery from the brain and liver as well as increased serum alanine aminotransferase levels. These studies highlight that CXCL10 expression promotes protection from coronavirus-induced neurological and liver disease.

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A Murine Virus (Jhm) Causing Disseminated Encephalomyelitis With Extensive Destruction of Myelin

Cited by 295 publications

References 2 publications

An immunodominant CD4+ T cell site on the nucleocapsid protein of murine coronavirus contributes to protection against encephalomyelitis

An immunodominant CD4+ T cell site on the nucleocapsid protein of murine coronavirus contributes to protection against encephalomyelitis

Adaptation of Coronavirus JHM to Persistent Infection of Murine Sac(-) Cells

Expression of CXC Chemokine Ligand 10 from the Mouse Hepatitis Virus Genome Results in Protection from Viral-Induced Neurological and Liver Disease

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