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Effect of persistent mouse hepatitis virus infection on MHC class I expression in murine astrocytes
1Department of Neurology, USC School of Medicine, Los Angeles 90033.
Abstract:
Neurotropic strains of mouse hepatitis virus (MHV) have been used extensively for the study of viral pathogenesis in the central nervous system (CNS), serving as models for human neurological diseases such as multiple sclerosis (MS). MHV strains A59 and JHMV both cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. In acute disease, CNS damage is most likely the result of lytic infection in neurons and oligodendrocytes, and death can be prevented by the adoptive transfer of Class I-restricted CD8+ T cells. However, in later stages of the disease induced by some MHV strains, virus tends to be restricted to astrocytes in a nonlytic infection, and the immune response appears to contribute to CNS damage. These data lead us to suggest that the astrocyte may play a central role in the neuropathogenesis of MHV infection. Consistent with this possibility, A59 has been reported to induce the expression of Class I molecules of the major histocompatibility complex (MHC) in glial cells following infection in vivo and in vitro. In this communication, we have examined the influence of persistent infection by both A59 and JHMV on MHC Class I expression in primary murine astrocytes. Persistence was characterized by the presence of intracellular viral antigen and mRNA in the absence of detectable infectious virus particles. Under these conditions, JHMV, but not A59, inhibited constitutive expression of the H-2 Kb molecule, with the magnitude of inhibition increasing with postinfection time. A59 was not able to induce Class I during persistence, presumably due to the lack of infectious virus particles. Class I expression was restored by the addition of gamma-interferon (IFN-gamma) to astrocytes persistently infected with either A59 or JHMV. Thus, Class I inhibition is not a permanent consequence of JHMV persistence, and persistence does not interfere with normal signalling pathways for Class I induction.
Insights
Mouse hepatitis virus (MHV) infection in astrocytes influences major histocompatibility complex (MHC) Class I expression. JHMV inhibits MHC Class I during persistent infection, but this is reversible with gamma-interferon.
Area of Science:
- Neurovirology
- Immunology
- Cellular Biology
Background:
- Neurotropic mouse hepatitis virus (MHV) strains model human CNS diseases like multiple sclerosis.
- MHV causes acute and chronic encephalomyelitis, with damage potentially linked to lytic infection and immune responses.
- Astrocytes may play a key role in MHV neuropathogenesis, particularly during persistent infections.
Purpose of the Study:
- To investigate the impact of persistent MHV infection on MHC Class I expression in primary murine astrocytes.
- To compare the effects of MHV strains A59 and JHMV on MHC Class I expression during persistent infection.
Main Methods:
- Primary murine astrocytes were persistently infected with MHV strains A59 and JHMV.
- MHC Class I expression (H-2 Kb molecule) was assessed during persistent infection.
- Gamma-interferon (IFN-γ) was added to evaluate restoration of Class I expression.
Main Results:
- Persistent JHMV infection, but not A59, inhibited constitutive MHC Class I (H-2 Kb) expression in astrocytes.
- The inhibition of Class I expression by JHMV increased with post-infection time.
- Addition of IFN-γ restored MHC Class I expression in astrocytes persistently infected with either MHV strain.
Conclusions:
- Persistent MHV infection, particularly by JHMV, can modulate MHC Class I expression in astrocytes.
- MHC Class I inhibition is not permanent and can be reversed by IFN-γ, indicating intact signaling pathways.
- Astrocytes' role in MHV neuropathogenesis may involve altered MHC Class I expression during persistent infection.