Regulation of JC virus by the POU-domain transcription factor Tst-1: implications for progressive multifocal leukoencephalopathy.
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.
Wegner
M
M
Eukaryotic Regulatory Biology Program, University of California, San Diego, La Jolla 92093-0648.
Drolet
D W
DW
Rosenfeld
M G
MG
D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006801:Humans; D066298:In Vitro Techniques; D007577:JC Virus / Q000235:genetics* / Q000254:growth & development; D007968:Leukoencephalopathy, Progressive Multifocal / Q000235:genetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D050816:Octamer Transcription Factor-6; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics; D015678:Viral Structural Proteins / Q000235:genetics
D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009838:Oligodeoxyribonucleotides; C494178:POU3F1 protein, human; D014157:Transcription Factors; D014764:Viral Proteins; D015678:Viral Structural Proteins; D050816:Octamer Transcription Factor-6