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 Vpr and Vpx present in HIV-2ROD particles. 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-2 Vpx, do not restrict its incorporation. Instead, the accumulation of HIV-2ROD Vpr 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.
Kewalramani
V N
VN
Fred Hutchinson Cancer Research Center, Division of Molecular Medicine, Seattle, Washington 98104, USA.
Park
C S
CS
Gallombardo
P A
PA
Emerman
M
M
D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D016336:Gene Products, vpr / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D015497:HIV-1 / Q000378:metabolism; D015498:HIV-2 / Q000737:chemistry* / Q000378:metabolism; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D011993:Recombinant Fusion Proteins; D013601:T-Lymphocytes; D054334:Viral Regulatory and Accessory Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D014771:Virion / Q000737:chemistry*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D011993:Recombinant Fusion Proteins; C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus