HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 CELL-CYCLE CONTROL - VPR IS CYTOSTATIC AND MEDIATES G(2) ACCUMULATION BY A MECHANISM WHICH DIFFERS FROMDNA-DAMAGE CHECKPOINT CONTROL

Vpr is a 96-amino-acid protein encoded by human immunodeficiency virus type 1 (HIV-1) that prevents proliferation of infected cells. We have established a system for infection of 100% of a T-cell population wit h HIV and use this system to show that within the context of HIV-1 inf ection, Vpr is primarily cytostatic rather than cytotoxic. Vpr acts up stream of dephosphorylation of the mitotic cyclin-dependent kinase, an d causes infected cells to accumulate in the G(2) stage of the cell cy cle. However, some HIV-1 infected cells increase in ploidy and size, a ccumulating DNA to an 8N level. Furthermore, the mechanism of the Vpr mitotic block is qualitatively different from that of G(2) DNA damage checkpoint control.