RESTRICTED INFECTION WITH CANINE-DISTEMPER VIRUS LEADS TO DOWN-REGULATION OF MYELIN GENE-TRANSCRIPTION IN CULTURED OLIGODENDROCYTES

Canine distemper virus (CDV) induces oligodendroglial degeneration and multifocal demyelination in the central nervous system. The mechanism of oligodendrocyte degeneration is not understood but it has been sho wn that there is a restricted infection of these cells without viral p rotein production. Using a combination of immunocytochemistry and in s itu hybridization we were able to demonstrate the transcription of the entire virus genome throughout the whole observation period (7-35 day s after infection) in oligodendrocytes in CDV-infected brain cell cult ures. Therefore, the lack of viral protein and particle production can not be explained on the basis of a defective viral transcription. The present study also shows that a restricted infection of oligodendrocy tes with CDV down-regulates the transcription of the major myelin gene s coding for proteolipid protein, myelin basic protein (MBP) and myeli n-associated glycoprotein in a very similar way. Using densitometry fo r in situ hybridization products of MBP in populations of normal and i nfected oligodendrocytes, an effect could be observed long before morp hological changes were detectable. The present results strongly sugges t that demyelination in distemper is induced by a restricted CDV infec tion of oligodendrocytes which down-regulates the expression of a vari ety of cellular genes, in particular those coding for myelin proteins. Consequently, the infected cells are no longer able to synthesize all the membrane compounds which are necessary for maintaining their stru ctural integrity.