COOPERATIVE ACTIONS OF HIV-1 VPR AND P53 MODULATE VIRAL GENE-TRANSCRIPTION

Transcription of the human immunodeficiency virus type-1 (HIV-1) genom e is controlled by cooperative interaction of viral encoded proteins a nd host regulatory proteins. In this study, we have examined the capac ity of the viral auxiliary protein, Vpr, to modulate transcriptional a ctivity of the HIV-1 promoter sequence located within the long termina l repeat (LTR), We demonstrate that ectopic expression of Vpr in human astrocytic cells, U-87MG, enhances the basal activity of the viral pr omoter in transfected cells and that the GC-rich sequences, spanning n ucleotides -80 to -43, are important for this activity. Since this reg ion serves as the target for p53-induced suppression of LTR activity a nd interacts with the ubiquitous transcription factor, Spl, we examine d the cooperative activity of Vpr, p53, and Spl upon LTR transcription . Results from co-transfection studies indicated that overexpression o f wild type p53, but not mutant p53, decreases the level of activation of the LTR by Vpr. Transcriptional activation of the LTR by Vpr requi red the presence of Spl since overexpression of Vpr in cells with no e ndogenous Spl failed to augment LTR activity. Results from protein-pro tein interaction studies indicated that Vpr is associated with both p5 3 and Spl in cells with ectopic expression of these proteins. Moreover , it was evident that p53 and Spl interact with each other in these ce lls. These functional and structural studies provided a working model on the cooperative interaction of Vpr with cellular proteins Spl and p 53 and control of viral gene transcription at immediate early stage of infection prior to the participation of other viral regulatory protei ns.