Regulation of the host range of human papovavirus JCV.

Human papovavirus JCV is associated with the human demyelinating disorder progressive multifocal leukoencephalopathy. In tissue culture, the virus is largely restricted to growth in primary human fetal glial cell. In this study, we demonstrate two levels of regulation of the viral host range. Expression of the early JCV mRNA, which encodes the essential viral protein, large tumor antigen (T antigen), depends on recognition of the early enhancer/promoter elements by tissue-specific factors found in both human and rodent glial cells. In the presence of JCV T antigen, viral DNA replication requires a species-specific factor, presumably a component of DNA polymerase, which is found in a wide range of primate cells. We further demonstrate that simian virus 40 T antigen has sufficient homology to efficiently substitute for the analogous JCV protein in initiating viral DNA replication.