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

The different effect of A59 and JHMV on class I expression in astrocytes suggests that class I may play different roles in their pathogenesis. As discussed by Maudsley et al. (73) , the classical picture of MHC expression after virus infection is that of an increase that is most likely mediated by the release of IFNs by infiltrating immune cells, and is thought to facilitate the ability of T cells to recognize the infected cells and control or eliminate the infection. Unfortunately, clearance of virus from infected tissue by CTLs is often accompanied by significant cellular destruction, which is not well tolerated in tissues with limited regenerative capacity, especially the CNS. Thus, the ability of a virus to stimulate class I expression in host cells may facilitate a rapid CTL response that in turn accelerates tissue destruction originally begun by virus-mediated cell lysis (74) . This may be the case for A59 infection, since the A59 strains used in these experiments cause a severe encephalitis after i.c. inoculation that begins on day 4 p.i., and results in death of the majority of infected mice by day 6-7 p.i. (our unpublished data). However, it is not known if the infiltration of T cells into the CNS after i.c. A59 infection is associated with the onset of encephalitis. By contrast, JHMV causes a similar clinical dis-ease, but the onset of encephalitis is delayed in comparison with that of A59, beginning on day 6-7 p.i. (21) . Death occurs on day 9-11 at a similar incidence. The onset of encephalitis coincides with the appearance of immune cells in the CNS, which, after JHM-DS infection, peaks on days 7-9 p.i. (75) . It is possible that class I expression is upregulated at this time by the secretion of interferon by the infiltrating immune cells, facilitating JHMV-specific, CTL-mediated tissue destruction. Thus, the difference in the ability of JHMV and A59 to stimulate class I expression in astrocytes may contribute to the speed of disease progression in the CNS. It is interesting to note that Fazakerley et al. (25) reported that the JHMV variant, V5A13.1, is neuroattenuated relative to parental JHMV by its slower rate of spread in the CNS of BALB/c mice. Variant V5A13.1 differs from parental JHMV by the deletion of 142 amino acids in one of the subunits of the S protein (16, 76) , suggesting that S plays an important role in the rate of virus spread in the CNS. In this respect, it would be of interest to test the ability of neuroattenuated A59 strains to stimulate class I expression in astrocytes.