THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VPR GENE ARRESTS INFECTED T-CELLS IN THE G(2)-CYCLE(M PHASE OF THE CELL)

Human immunodeficiency virus type 1 (HIV-1) infection causes profound immunological defects in afflicted patients. Various mechanisms have b een proposed to account for the immune dysfunction in AIDS ultimately leading to loss of CD4(+) T cells, including HIV-1 envelope-mediated s yncytium formation, apoptosis, and cytokine modulation. Here we presen t results which suggest a novel hypothesis for T-cell dysfunction. We show, using HIV-1 bearing a novel cell surface reporter gene, that inf ected cells are unable to progress normally through the cell cycle and became arrested in the G(2) + M phase. Furthermore, we identify the H IV-1 vpr gene product as being both necessary and sufficient for elici ting this cell cycle arrest. Cell cycle arrest induced by Vpr correlat es with an increase in the hyperphosphorylated (inactive) form of the cyclin-dependent serine/threonine kinase CDC2, consistent with an arre st of cells at the boundary of G(2) and M.