TRANSCRIPTIONAL REGULATION - LESSONS FROM THE HUMAN NEUROTROPIC POLYOMAVIRUS, JCV

The human demyelinating disorder, progressive multifocal leukoencephal opathy (PML), is attributed to a lytic infection of myelin-producing o ligodendrocytes by the human polyoma JC virus (JCV) (reviewed in Frisq ue and White, 1992; Major at al., 1992). Like other polyoma viruses, J CV has a closed, circular, supercoiled double-stranded DNA genome. The JCV genome can be structurally divided into th ree fu notional region s - the early coding region (encoding the regulatory proteins, the lar ge T, and the small t antigens) located on the proximal side of the re plication origin, the late coding region (encoding the structural prot eins VP1, VP2, and VP3 and the agno-protein) located on the distal sid e of the replication origin, and the noncoding or regulatory region (c ontaining the origin of viral DNA replication and the transcriptional control region) that lies between the two coding regions (Pig. 1A) (Fr isque and White, 1992). The JCV noncoding region functions in opposite orientations to regulate expression from the early and late gene codi ng regions. This review offers a comprehensive guide to the transcript ional regulation of JCV gene expression.