Coronavirus induction of class I major histocompatibility complex expression in murine astrocytes is virus strain specific

After intracerebral (i.c.) inoculation in mice and rats, the parent strains of both JHMV and A59 cause an acute encephalomyelitis and demyelination from which a varying number of animals survive to exhibit chronic demyelination (1) (2) (3) (4) (5) (6) (7) 11) . The severity of the disease varies with the individual virus strain and with the age, genetic background, and immune status of the infected host. The neuropathological features of acute infection can be somewhat distinguished from those of chronic disease by a prevalence of gray matter involvement in which virus replicates in neurons, oligodendrocytes, and astrocytes to cause extensive CNS damage (18) (19) (20) (21) . In chronic disease, lesions are more prevalent in the white matter and consist of primary demyelination with axonal sparing (2, 11) . Infectious virus is rarely isolated during chronic JHMV disease, though viral RNA can be detected by reverse transcriptase (RT)-PCR in the brains of infected mice as late as 2 yr post infection (p.i., Fleming, J., personal communication). Viral antigen and RNA tend to be restricted to astrocytes in chronic infection (2, (22) (23) (24) (25) , though there is evidence that neurons are also affected (25) . This pattern of white matter involvement is also characteristic of infection with attenuated or mutant strains of A59 (26, 27) or JHMV (25, (27) (28) (29) , which cause demyelination in the relative absence of encephalitis. In vitro, JHMV and A59 cause a lytic infection in primary oligodendrocyte cultures that is rapidly selflimiting, but both virus strains can establish a productive and relatively nonlytic, acute, and long-term chronic infection in mixed glial cell cultures and in cultures enriched for astrocytes (30) (31) (32) . These data support early reports that acute demyelination is the result of virus-mediated oligodendrocyte death (2, 11) , but more importantly, they also suggest that the astrocyte plays an important role in acute encephalitis and chronic demyelination.