Regulation of JC virus by the POU-domain transcription factor Tst-1: implications for progressive multifocal leukoencephalopathy

Abstract

Progressive multifocal leukoencephalopathy results from an opportunistic infection of myelin-producing oligodendrocytes by the glia-specific human papovavirus JC. In this report, evidence is presented that the glial transcription factor Tst-1, a member of the POU-domain family, stimulates transcription of both early and late viral genes. Stimulation was dependent on site-specific binding of Tst-1 to the JC viral regulatory region and on the presence of an intact amino-terminal transactivation domain within Tst-1. Because of its ability to increase the expression of viral large tumor antigen, Tst-1 stimulated viral DNA replication, without participating directly in the replication event. Our results suggest that Tst-1 is one of the determining factors in the glia specificity of JC virus.