HIV-1 VIRAL-PROTEIN-R (VPR) REGULATES VIRAL REPLICATION AND CELLULAR PROLIFERATION IN T-CELLS AND MONOCYTOID CELLS IN-VITRO

Among the putative accessory genes of HIV-1, the 96-amino-acid virion- associated vpr gene product has been described to have several novel b iological activities, These include cytoplasmic-to-nuclear translocati on, which empowers HIV to infect and replicate in non-dividing cells a nd to increase viral replication, particularly in macrophages. Alone; with these viral effects, we found that HIV-1 Vpr induces dramatic bio logical changes in the target cells of HIV infection, including induct ion of changes in transcriptional patterns, morphological changes, and complete inhibition of proliferation, which collectively was termed d ifferentiation, These changes occur in the absence of other viral gene products, suggesting that Vpr mediates its proviral effects partially or perhaps solely through modulation of the state of the target cell rather than directly on the virus, The inhibition of proliferation in T cell lines has been extended by several groups to demonstrate that t he inhibition of proliferation is through G2 cell cycle arrest, furthe r supporting the idea that Vpr acts directly on cellular targets, We h ave recently described a role for Vpr in modulating the glucocorticoid pathway, which is involved in the regulation of the state of the cell , in cytoplasmic-to-nuclear translocation, and in modulation of host c ell transcription, It is important to note that certain antiglucocorti coid compounds modulate Vpr activity in vitro, These results support t he idea that the host cell contains specific receptor molecule(s) thro ugh which Vpr mediates its activity, Consequently, Vpr represents a un ique-target for anti-HIV drug development and has significance for HIV -1 disease progression.