Protein Stability Influences Human Immunodeficiency Virus Type 2 Vpr Virion Incorporation and Cell Cycle Effect

Abstract

Using recombinant proteins as standards, we calculated the amount of Vpr and Vpx present in HIV-2RODparticles. We find 2000–3000 copies of Vpx per particle but only 40–50 copies of Vpr. We investigated the reasons for this discrepancy between Vpx and Vpr and found that viral factors, including HIV-2Vpx, do not restrict its incorporation. Instead, the accumulation of HIV-2RODVpr during infection is restricted by a short protein half-life which acts to limit its virion incorporation. The half-life of HIV-2 Vpr was calculated to be about 90 min, while 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 accumulate in G2 of the cell cycle, the effect of HIV-2 Vpr is attenuated relative to HIV-1 Vpr. Thus, protein stability correlates with both the function of Vpr and its virion incorporation.