In vivo and in vitro models of demyelinating diseases. XV. Differentiation influences the regulation of coronavirus infection in primary explants of mouse CNS

Abstract

Mouse oligodendrocytes and astrocytes, in primary cerebral explant cultures, were infected with JHMV and MHV3 coronaviruses. Contrary to previous findings with neural cells from the rat (S. Beushausen and S. Dales, 1985, Virology 141, 89-101), these agents show no discrimination in the tropism and have the ability to replicate in either type of murine glial cell. Effects of the differentiation inducer dbcAMP on levels of the myelinspecific enzyme 2':3'-cyclic nucleotide-3'-phosphohydrolase (CNPase) activity and virus replication were determined. In the mouse system there was a gradual, continuous elevation of CNPase beyond 30 days whereas in comparable rat cell cultures maximum CNPase enhancement is elicited within 21 days (F. A. McMorris, 1983, J. Neurochem. 41, 506-515). After dbcAMP treatment replication of both coronaviruses was profoundly suppressed in murine oligodendrocytes, consistent with our findings on JHMV replication in treated rat oligodendrocytes. By contrast the replication of JHMV and MHV3 in dbcAMP-treated murine astrocytes was influenced only marginally. These findings provide further support for the hypothesis that susceptibility of rodents to CNS infection by coronaviruses is determined, in part, by the age-related maturation process of oligodendrocytes.