Mouse hepatitis virus A59 increases steady-state levels of MHC mRNAs in primary glial cell cultures and in the murine central nervous system.
Infection of mixed glial cell cultures with mouse hepatitis virus (MHV)-A59 results in an approximately six-fold increase in the level of major histocompatibility complex (MHC) class I mRNA. In situ hybridization of glial cell cultures infected with MHV-A59 again showed enhanced MHC mRNA expression, both in infected and uninfected cells. These results extend our earlier finding that MHC surface antigens are enhanced on astrocytes and oligodendrocytes after MHV-A59 infection and suggest that this enhancement is a result of an increase in the steady-state level of MHC mRNA. We further demonstrate that increases in MHC mRNA occur in the murine central nervous system (CNS) following infection in vivo. Northern blot analysis of RNA from the brains of infected animals showed transient expression of both MHC class I and class II mRNA over the first 14 days of infection. Expression coincided with viral replication and clearance. In situ hybridization of brain sections from infected animals showed that class I and class II expression was widespread throughout all portions of the brain and in uninfected as well as infected cells. Viral RNA, in contrast, was observed in small foci of cells and mostly within the limbic system. Thus enhancement of MHC mRNA was not restricted either to areas of infection or inflammation. The spatial relationship between viral and MHC expression supports our hypothesis that a soluble mediator is involved in the mechanism of the increase in MHC levels. The fact that MHC induction occurs in vivo as well as in vitro suggests MHC may be important in the mechanism of MHV-induced disease.
Gombold
J L
JL
Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia 19104.
Weiss
S R
SR
D000818:Animals; D001921:Brain / Q000276:immunology; D002460:Cell Line; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006524:Hepatitis, Viral, Animal / Q000276:immunology*; D017403:In Situ Hybridization; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000254:growth & development / Q000276:immunology*; D009457:Neuroglia / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification
D012333:RNA, Messenger