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

In this communication, we report that the ability of A59 to stimulate MHC class I expression during acute infection in primary murine astrocytes, previously observed by Suzumura et al. (33, 53, 54) , is not an inherent property of MHV strains. It is interesting to note that the strains that did not stimulate class I are derivatives of the highly neurotropic MHV-4, or JHMV strain, whereas most of the MHV strains that did are the more hepatotropic strains. However, class I-inducing in JHMV was also not due to poor replication efficiency in astrocytes, since JHMV infected the same percentage of cells and produced similar levels of infectious virus as the class I-inducing MHV strains (Table 3) . Thus, some other MHV characteristic must be responsible for class I-inducing activity, or the lack thereof. Since the expression of class I genes is regulated by interferons (55) , it seemed possible that class I induction might correlate with the ability of MHV strains to stimulate IFN production. This possibility gains credibility from reports that JHMV is a notoriously poor inducer of interferon after in vitro (56) and in vivo (57) infection. However, Suzumura et al. (53) did not detect IFNs in UV-treated supernatants from A59-infected mixed glial cells in spite of the presence of class I-inducing activity, and our findings indicate that A59-induced class I expression was not inhibited by antibodies to IFN-a/3 or -3' (Table 4 ). Unlike Suzumura et al. (53), we did not find that class I-inducing activity was retained after UV-inactivation of A59 or the A59-1ike recombinant MHV strains (Table 4) , and it was not detected in supernarants from A59-infected astrocytes that were UV-treated to inactivate infectious virus (Table 5 and Fig. 5 ). In addition, we have recently found that class I expression is no longer observed when A59 replication is controlled by the culture of persistently infected astrocytes in the presence of MHVspecific polyclonal antiserum, in spite of the persistence of viral protein and RNA (58) . Overall, our data suggest that class I induction by MHV in astrocytes requires infectious virus and does not involve the secretion of a soluble factor. In this respect, it is interesting to note that the class I-inducing activity originally reported by Suzumura et al. (33, 53) was also dependent on continuous virus production in glial cell cultures prepared from the brains of infected mice (54) . However, it is possible that our lack of detection of class I-inducing activity in the supernatants could reflect culture, or other technical conditions. Although it was not possible to attribute class I-inducing activity to a single gene or gene product using the A59/JHMV recombinant virus strains, the data clearly indicate that class I-inducing activity maps to the 3' end of the A59 genome, which contains the genes encoding the primary structural proteins S, M, and N, and two poorly understood nonstructural proteins. However, there are some indications that S is the most likely candidate. For example, recombinant strains which retain more A59 sequences in the S gene tended to be more potent than those retaining less A59, or moreJHMV character. In addition, the S gene shows the greatest antigenic divergence of the structural proteins between A59 and JHMV (12) (13) (14) (15) (16) and so might be more likely to exhibit differences in activity. This possibility is supported by data indicating that A59 andJHMV differ considerably in their ability to