Human immunodeficiency virus type I Vpr gene product prevents cell proliferation on mouse NIH3T3 cells without the G(2) arrest of the cell cycle

Human immunodeficiency virus type 1 Vpr is a 96-amino-acid virion-associated protein that arrests cells in the G(2) phase of the cell cycle in peripheral blood lymphocytes, HeLa, 293, 293T, A549, Jurkat, CEM, SupT1, CV-1 and COS1 cells. When we transfected Vpr expression vector into mouse NIH3T3 and then cultured it in the presence of G418, NIH3T3 cells were the drug resistant cells yielded. The surviving colonies, however, exhibited a degenerating morphology up to 8 similar to 20-fold smaller than the control vector colonies. In addition, the growth of NIH3T3 cells transiently transfected viith Vpr expression vector declined dramatically compared with that of transfectants with control vector, suggesting that Vpr significantly interferes with cell proliferation of NIH3T3 cells. Cell cycle characterization by flow cytometry indicated that expression of Vpr did not induce G(2) cessation in NIH3T3. These findings strongly suggest that Vpr has a novel pathway to retard cell growth independently and arrests the G(2) phase of the cell cycle. (C) 1997 Academic Press.