translation agency

The HIV-1 viral protein R (Vpr) influences HIV-1 replication through regulation of the cell.
Ayyavoo V; Mahalingham S; Refaeli Y; Levy D; Williams WV; Weiner DB;
November 30, 1996
3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:171. Unique

Among the putative accessory genes of HIV-1 the 96 amino acid viral bornevpr gene product has been described to have several novel biological activities. These include cytoplasmic to nuclear translocation thus empowering HIV to infect and replicate in non dividing cells and to function to increase viral replication particularly in monocytes. Along with these viral effects we described that HIV-1 Vpr induces dramatic biological changes in the target cells of HIV infection including induction of changes in transcriptional patterns and complete inhibition of proliferation in which collectively was termed differentiation. These changes occur in the absence of other viral gene products and suggested that Vpr mediates its pro-viral effects partially or perhaps solely through modulation of the state of the target cell rather than directly on the virus. The inhibition of proliferation T cell lines has been extended by several groups to demonstrate that the inhibition of proliferation is specifically at the G2 border of the cell further supporting the Vpr activity is directed at cellular targets. A role for Vpr in modulating the Glucocorticoid pathway has recently been described and anti-glucocorticoids modulate Vpr activity. These results demonstrate that the cell contains specific receptor(s) molecule(s) through which Vpr mediates its activity and these molecules have implications for cell biology in general. Studies to define the molecules involved in Vpr activity and the relationships between these observations and Vpr activity in primary cell lines will be presented. Vpr represents a unique target for anti-HIV drug development and has significance of HIV-1 disease progression.

Cell Differentiation G2 Phase Gene Products, vpr/*PHYSIOLOGY HIV Infections/PATHOLOGY HIV-1/GENETICS/*PHYSIOLOGY Transcription, Genetic Virus Replication/*PHYSIOLOGY ABSTRACT