Expression of viral and myelin gene transcripts in a murine CNS demyelinating disease caused by a coronavirus

C57BI/6N mice develop a CNS demyelinating disease when inoculated intracranially at 4 weeks of age with the A59 strain of mouse hepatitis virus (MHV-A59). In order to explore the virus-host interactions, the histological features of the demyelinating disease were correlated with the spatial and temporal distribution of viral transcripts and the expression of oligodendrocyte-specific genes (myelin basic protein, proteolipid protein, myelin-associated glycoprotein, and 2',3' cyclic nucleotide 3'-phosphohydrolase) in the spinal cord of diseased mice. Three distinct phases in the disease were identified. In the first phase, 1 week postinfection (1 WPI), virus replication was widespread in both gray and white matter but was preferentially occurring in glial cells. In the ventral and dorsal root zones where viral transcripts were most abundant, all myelin gene transcripts were decreased before demyelination was seen. During the second phase of the disease (2-3 WPI), viral transcripts decreased in abundance and became restricted to the white matter. Numerous demyelinating lesions were observed and were characterized by inflammatory cells, paucity of oligodendrocytes, and a profound decrease of all myelin gene transcripts. In the third phase of the disease (4-6 WPI) no viral transcripts were detected, and remyelination began. In the lesions and the tissue surrounding them, transcripts of all myelin genes increased to levels above normal. The increased expression of myelin gene transcripts occurred in a synchronized manner and with a cellular distribution reminiscent of that seen in developmental myelination. These molecular events correlated with efficient remyelination and clinical recovery in this murine demyelinating disease.