VPR-INDUCED CELL-CYCLE ARREST IS CONSERVED AMONG PRIMATE LENTIVIRUSES

We previously reported that expression of human immunodeficiency virus type 1 strain NL4-3 (HIV-1(NL4-3)) vpr causes cells to arrest in the G(2) phase of the cell cycle. We examined the induction of cell cycle arrest by other HIV-1 isolates and by primate lentiviruses other than HIV-1. We demonstrate that the vpr genes from tissue culture-adapted o r primary isolates of HIV-1 are capable of inducing G(2) arrest. In ad dition, we demonstrate that induction of cell cycle arrest is a conser ved function of members of two other groups of primate lentiviruses, H IV-2/simian immunodeficiency virus strain sm (SIVsm)/SIVmac and SIVagm , vpr from HIV-1, HIV-2, and SIVmac induced cell cycle arrest when tra nsfected in human (HeLA) and monkey (CV-1) cells. vpx from HIV-2 and S IVmac did not induce detectable cell cycles arrest in either cell type , and SIVagm vpx was capable of inducing arrest in CV-1 but not HeLa c ells. These results indicate that induction of cell cycle perturbation is a general property of lentiviruses that infect primates. The conse rvation of this viral function throughout evolution suggests that it p lays a key role in virus-host relationships, and elucidation of its me chanism may reveal important clues about pathology induced by primate lentiviruses.