In vivo and in vitro models of demyelinating disease. Possible relationship between induction of regulatory subunit from cAMP dependent protein kinases and inhibition of JHMV replication in cultured oligodendrocytes.

Abstract

The results in this study suggest a unique possible association between inhibition of JHMV replication and the induction of R1 proteins in differentiating oligodendrocytes, involving inhibition of a PPPase found in the endosome fractions of cells. Free R1 protein appears to prevent the dephosphorylation of purified JHMV-NC substrate thereby possibly blocking the normal sequence of events necessary for NC release of viral genomes. Inhibition of host-cell endosome PPPase's may have relevance to controlling JHMV infection since CV particles adsorbing to cell surface receptors are believed to penetrate via clathrin coated pits into endosomes. Thus, the early stages of CV infection, including dephosphorylation of NC protein within endosomes, provide a possible site for controlling the initial stages of viral infection.