Journal of General Virology, Vol 79, 2147-2155, Copyright © 1998 by Society for General Microbiology
T-antigen-dependent transcriptional initiation and its role in the regulation of human neurotropic JC virus late gene expression
GV Raj, GL Gallia, CF Chang and K Khalili
Center for NeuroVirology and NeuroOncology, Allegheny University of the Health Sciences, Philadelphia, PA 19102, USA.
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.
