The protective role of cytotoxic T cells and interferon against coronavirus invasion of the brain.

Abstract

MHV-A59 causes focal acute encephalitis, acute hepatitis, and chronic demyelination while MHV-2 causes acute hepatitis and no brain involvement. The difference in organ tropism between these two closely related MHVs is not related to the ability of these viruses to grow in brain cells since both viruses grow equally well in primary glial cell cultures derived from neonatal mouse brains. We postulated therefore that the ability of the virus to stimulate certain host immunological factors may be important for protection of the brain against invasion and replication of the virus. In this study we performed preliminary experiments to investigate the potential role of two host factors in protection of the brain against MHV invasion: cytotoxic T cells and interferon. Four week old beta 2M(-/-) mice, lacking beta 2 microglobulin, MHC class I expression and functional cytotoxic CD8+ T cells were inoculated intracerebrally (IC) with MHV-2 and analyzed at various intervals post infection for histopathology and viral titers in organs. Histology revealed both acute hepatitis and acute encephalitis. Acute encephalitis was observed in periventricular areas. Mononuclear lymphocytic infiltration involved the choroid plexus, the ependyma and in the surrounding brain parenchyma. There was no involvement of other areas of the brain including areas that are typically involved in A59 infection of C57B1/6 mice. By contrast, C57b1/6 mice infected with MHV-2 showed no involvement of the brain parenchyma and only slight inflammation of the choroid plexus was present. High titers of infectious virus was detected by plaque assay in both brains and livers of beta 2M(-/-) mice infected with MHV-2 in contrast to only liver titers in C57B1/6 mice infected with a similar dose of MHV-2.(ABSTRACT TRUNCATED)