HIV-1 VPR INCREASES VIRAL EXPRESSION BY MANIPULATION OF THE CELL-CYCLE - A MECHANISM FOR SELECTION OF VPR IN-VIVO

The human immunodeficiency virus type 1 (HIV-1) encodes a protein, cal led Vpr, that prevents proliferation of infected cells by arresting th em G(2) of the cell cycle. This Vpr-mediated cell-cycle arrest is also conserved among highly divergent simian immunodeficiency viruses, sug gesting an important role in the virus life cycle. However, it has bee n unclear how this could be a selective advantage for the virus. Here we provide evidence that expression of the viral genome is optimal in the G(2) phase of the cell cycle, and that Vpr increases virus product ion by delaying cells at the point of the cell cycle where the long te rminal repeat (LTR) is most active. Although Vpr is selected against w hen virus is adapted to tissue culture, we show that selection for Vpr function in vivo occurs in both humans and chimpanzees infected with HIV-1. These results suggest a novel mechanism for maximizing virus pr oduction in the face of rapid killing of infected target cells.