PROTEIN STABILITY INFLUENCES HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 VPR VIRION INCORPORATION AND CELL-CYCLE EFFECT

Using recombinant proteins as standards, we calculated the amount of V pr and Vpx present in HIV-2(ROD) particles. We find 2000-3000 copies o f Vpx per particle but only 40-50 copies of Vpr. We investigated the r easons for this discrepancy between Vpx and Vpr and found that viral f actors, including HIV-2 Vpx, do not restrict its incorporation. Instea d, the accumulation of HIV-2(ROD) Vpr during infection is restricted b y a short protein half-life which acts to limit its virion incorporati on. The half-life of HIV-2 Vpr was calculated to be about 90 min, whil e HIV-2 Vpx and HIV-1 Vpr had half-lifes of 36 and 20 hr, respectively . Moreover, while both HIV-1 Vpr and HIV-2 Vpr cause cells to accumula te in G2 of the cell cycle, the effect of HIV-2 Vpr is attenuated rela tive to HIV-1 Vpr. Thus, protein stability correlates with both the fu nction of Vpr and its Virion incorporation. (C) 1996 Academic Press, I nc.