Gombold J L, Weiss S R
Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia 19104.
Microb Pathog. 1992 Dec;13(6):493-505. doi: 10.1016/0882-4010(92)90015-g.
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.
用小鼠肝炎病毒（MHV）-A59感染混合神经胶质细胞培养物会导致主要组织相容性复合体（MHC）I类mRNA水平增加约6倍。对感染了MHV-A59的神经胶质细胞培养物进行原位杂交，结果再次显示，无论是感染细胞还是未感染细胞，MHC mRNA表达均增强。这些结果扩展了我们之前的发现，即MHV-A59感染后星形胶质细胞和少突胶质细胞表面的MHC抗原会增强，这表明这种增强是MHC mRNA稳态水平增加的结果。我们进一步证明，在体内感染后，小鼠中枢神经系统（CNS）中会出现MHC mRNA增加。对感染动物大脑RNA的Northern印迹分析显示，在感染的前14天，MHC I类和II类mRNA均有短暂表达。这种表达与病毒复制和清除同时发生。对感染动物脑切片进行原位杂交显示，I类和II类表达在大脑所有部位的未感染细胞和感染细胞中均广泛存在。相比之下，病毒RNA在小细胞灶中观察到，主要在边缘系统内。因此，MHC mRNA的增强并不局限于感染或炎症区域。病毒表达与MHC表达之间的空间关系支持了我们的假设，即一种可溶性介质参与了MHC水平升高的机制。MHC诱导在体内和体外均会发生，这一事实表明MHC可能在MHV诱导疾病的机制中起重要作用。
