THE SV40 CAPSID PROTEIN VP3 COOPERATES WITH THE CELLULAR TRANSCRIPTION FACTOR SP1 IN DNA-BINDING AND IN REGULATING VIRAL PROMOTER ACTIVITY

Chromatin structure and protein-protein interactions play an important role in eukaryotic gene function. Nucleosomal rearrangement at the si mian virus 40 (SV40) regulatory region occurs at the late stages of th e viral life cycle preceding viral assembly. The SV40 capsid proteins are required for this nucleosomal rearrangement suggesting that they p articipate in turning-off the viral promoters. In aiming to elucidate the role of the capsid proteins in gene regulation, we studied the int eraction between VP3, an internal capsid protein, and the cellular tra nscription factor Spl, a major regulator of both the early and late vi ral promoters. Our results showed that VP3 repressed transcription fro m the viral early promoter in vitro. We found significant cooperativit y between Spl and VP3 in specific DNA-binding to the Spl binding site. Ln addition, protein-protein interactions between VP3 and Sp1 in the absence of DNA were observed. These findings have led us to conclude t hat the novel host-viral Sp1-VP3 complex down regulates viral transcri ption and further suggest that Sp1 participates in recruiting VP3 to t he SV40 minichromosome in SV40 assembly. (C) 1998 Academic Press Limit ed.