The Role of Vpr in the Regulation of HIV-1 Gene Expression

Abstract

Expression of the viral protein R, Vpr, of HIV-1 affects many biological events in host cells including cell cycle progression, and modulates HIV-1 gene transcription. Earlier studies implicated the cellular protein p21WAF1 (p21) in regulating HIV-1 transcription, which led us to investigate the functional and physical interaction of Vpr and p21. Our results show that Vpr modestly activated HIV-LTR in cells lacking p21 gene. We described the mechanisms of p21 and Vpr interaction for stimulating transcription of HIV-1. Data from the protein-protein interaction experiments revealed the ability of Vpr, p21 and p300 to form a complex. Further, we showed that, Vpr interacted with the N- and the C-terminal domains of p21. Furthermore, in cells expressing Vpr, p21 localizes to both the cytoplasm and the nucleus. Additionally, expression of Vpr alleviates p21-mediated inhibition of cell departure from G1 phase. Expression of a mutant Vpr, with arginine 73 altered to serine, did not affect p21 ability to cause cell arrest or its sub- cellular localization. These observations revealed a new cellular partner for Vpr, and provided a new therapeutic avenue for controlling HIV-1 expression.