CORONAVIRUS INDUCTION OF CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX EXPRESSION IN MURINE ASTROCYTES IS VIRUS-STRAIN SPECIFIC

Neurotropic strains of mouse hepatitis viruses (MHV) such as MHV-A59 ( A59) and MHV-4 (JHMV) cause acute and chronic encephalomyelitis and de myelination in susceptible strains of mice and rats. They are widely u sed as models of human demyelinating diseases such as multiple scleros is (MS), in which immune mechanisms are thought to participate in the development of lesions in the central nervous system (CNS). The effect s of MHV infection on target cell functions in the CNS are not well un derstood, but A59 has been shown to induce the expression of MHC class I molecules in glial cells after in vivo and in vitro infection. Chan ges in class I expression in infected cells may contribute to the immu nopathogenesis of MHV infection in the CNS. In this communication, a l arge panel of MHV strains was tested for their ability to stimulate cl ass I expression in primary astrocytes in vitro. The data show that th e more hepatotropic strains, such as MHV-A59, MHV-1, MHV-2, MHV-3, MHV -D, MHV-K, and MHV-NuU, were potent inducers of class I expression in astrocytes during acute infection, measured by radioimmunoassay. The K -b molecule was preferentially expressed over D-b. By contrast, JHMV a nd several viral strains derived from it did not stimulate the express ion of class I molecules. Assays of virus infectivity indicated that t he class I-inducing activity did not correlate with the ability of the individual viral strain to replicate in astrocytes. However, exposure of the viruses or the supernatants from infected astrocytes to ultrav iolet light abolished the class I-inducing activity, indicating that i nfectious virus is required for class I expression. These data also su ggest that class I expression was induced directly by virus infection, and not by the secretion of a soluble substance into the medium by in fected astrocytes. Finally, analyses of A59/JHMV recombinant viral str ains suggest that class I-inducing activity resides in one of the A59 structural genes.