T-antigen-dependent transcriptional initiation and its role in the regulation of human neurotropic JC virus late gene expression

Ganesh V. Raj, Gary L. Gallia, Chun Fan Chang, Kamel Khalili

Research output: Contribution to journalArticle

Abstract

The multifunctional protein of papovaviruses, T-antigen, regulates the virus lytic cycle partly by exerting transcriptional control over viral and cellular gene expression. In this study, the ability of the T-antigen of human neurotropic JC virus (JCV) to enhance expression from the virus late promoter has been further examined. By deletion analysis, a T-antigen-responsive region was mapped within the JCV 98 bp enhancer/promoter between nucleotides 139 and 168. Interestingly, T-antigen appears to mediate transactivation by increasing expression from a basal transcriptional initiation site and through a novel T-antigen-dependent initiation site (TADI). The TADI element contains a region homologous to initiator (Inr) sequences and is sufficient to confer T-antigen responsiveness to a heterologous minimal promoter. Electrophoretic mobility shift and UV crosslinking analyses demonstrate that multiple cellular proteins interact with both single- and double-stranded forms of this sequence. Mutations within the TADI element which abolish T-antigen-mediated transcriptional activation also prevent the formation of specific nucleoprotein complexes. These data suggest that the ability of JCV T-antigen to regulate JCV late gene expression may be partly due to the formation of specific nucleoprotein complexes and transcriptional initiation from the TADI site on the viral promoter.

Original languageEnglish (US)
Pages (from-to)2147-2155
Number of pages9
JournalJournal of General Virology
Volume79
Issue number9
DOIs
StatePublished - Sep 1998
Externally publishedYes

ASJC Scopus subject areas

  • Virology

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