Demyelination Determinants in the S Gene of MHV

Abstract

Demyelination is the hallmark pathologic process of several viral-induced, and inflammatory, immune-mediated diseases of the central nervous system (Allen and Bradkin 1993). Several experimental animal model systems are used to study demyelination, including MHV-induced demyelination in mice (Stohlman et al 1981; Wege et al 1982; Lavi et al 1984; Lavi et al 1984b; Lavi and Weiss 1989; Houtman et al 1996; Lavi et al 1999). Previous studies with this model suggested that the S protein and gene may be important for pathogenesis since the spike (S) protein participates in many functions related to virus-host interactions (Dalziel et al 1986). Thus we wanted to explore the possibility that the S gene contains molecular determinants of demyelination. We used targeted RNA recombination as previously described (Peng et al 1995; Leparc-Goffart et al 1998; Phillips et al 1999) to insert the S gene of a non-demyelinating virus (MHV-2) into the background of a demyelinating virus (MHV-A59). We then studied the pathogenesis of the new recombinant viruses.