HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VPR ARRESTS THE CELL-CYCLE IN G(2) BY INHIBITING THE ACTIVATION OF P34(CDC2)-CYCLIN-B

Human immunodeficiency virus type 1 (HIV-1) vpr inhibits the replicati on of tumor cell lines and peripheral blood mononuclear cells. Here it is demonstrated that expression of vpr, either in the context of a pr ovirus or from an independent genetic element, induces a discrete cell cycle arrest, with cells containing 4N DNA. Low cyclin B-associated k inase activity, as well as the status of p34(cdc2) and cdc25C phosphor ylation, indicates that the cascade of reactions which drives the cell into mitosis has not been initiated, The phosphatase inhibitor okadai c acid releases the block, suggesting that Vpr perturbs upstream regul ators of the G(2)-M transition. These studies demonstrate that HIV-1 v pr has profound effects on the cellular factors which control entry in to mitosis and indicate vpr's potential contribution to the cellular p athology associated with HIV-1 infection.