T-ANTIGEN-DEPENDENT TRANSCRIPTIONAL INITIATION AND ITS ROLE IN THE REGULATION OF HUMAN NEUROTROPIC JC VIRUS LATE GENE-EXPRESSION

The multifunctional protein of papovaviruses, T-antigen, regulates the virus lytic cycle partly by exerting transcriptional control over vir al and cellular gene expression. In this study, the ability of the T-a ntigen of human neurotropic JC virus (JCV) to enhance expression from the virus late promoter has been further examined. By deletion analysi s, a T-antigen-responsive region was mapped within the JCV 98 bp enhan cer/promoter between nucleotides 139 and 168, Interestingly, T-antigen appears to mediate transactivation by increasing expression from a ba sal transcriptional initiation site and through a novel I-antigen-depe ndent initiation site (TADI), The TADI element contains a region homol ogous to initiator (Inr) sequences and is sufficient to confer T-antig en 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-a ntigen-mediated transcriptional activation also prevent the formation of specific nucleoprotein complexes. These data suggest that the abili ty of JCV T-antigen to regulate ICV late gene expression may be partly due to the formation of specific nucleoprotein complexes and transcri ptional initiation from the TADI site on the viral promoter.