CD8 T Cell Mediated Immunity to Neurotropic MHV Infection
Neurological disease induced by neurotropic coronaviruses has received considerable attention not only as a model for virus induced demyelination, but also of immune regulation and viral persistence within the central nervous system (CNS). The neurotropic JHM strain (JHMV) of mouse hepatitis virus (MHV) produces an acute CNS infection characterized by encephalomyelitis and demyelination. Several strains and variants have been derived from the lethal, parental JHMV to better study the demyelinating process as a subacute disease resembling the human CNS disease, Multiple Sclerosis. A concise overview of historical aspects, derivation of neurotropic Coronavirus strains and variants, together with types of neurological disease and immune responses associated with these viruses is provided in the previous volume of this series (Perlman, 1998) and in several other recent reviews (Houtman and Fleming 1996, Lane and Buchmeier 1997, Stohlman et al 1999). Advances in molecular immunology techniques, combined with the use of selective exclusion of immune components, either using antibody (Ab) mediated depletion or genetic disruption, has resulted in significant progress in dissecting the interactions between virus, CNS cells, and immune responses and their role in demyelination. This chapter therefore focuses on advances of the past 3-4 years in elucidating interactions between CNS infection and immune responses leading to persistence. As MHV variants differ vastly in tropism, spread, clinical symptoms and mortality, this review focuses largely on a murine model of infection using the neuroattenuated 2.2v-l variant of JHMV (Fleming et al 1986). This mAb selected variant establishes a persistent infection associated with extensive, subacute, ongoing CNS demyelination in the absence of infectious virus. During acute infection this virus replicates primarily in microglia, astrocytes and oligodendrocytes. Although the immune response of immunocompetent hosts generally eliminates infectious virus within 14 days post infection (p.i.), survivors remain persistently infected as evidenced by the detection of viral RNA (vRNA). Despite suffering from varying degrees of encephalitis and paralysis during acute infection, mice generally recover from clinical symptoms and remain asymptomatic during viral CNS persistence.
KeywordsInfected Mouse Cell Mediate Immunity Infectious Virus Central Nervous System Infection Viral Clearance
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