CHARACTERIZATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VIF PARTICLE INCORPORATION

The human immunodeficiency virus type 1 (HIV-1) Vif protein is necessa ry at the time of viral particle formation yet functionally manifests its effect after virions enter target cells. This suggests that Vif ei ther acts on another viral protein or is itself incorporated into part icles. In this study, we have examined the latter possibility. We conf irm our previous observation that Vif is incorporated into human immun odeficiency virus type 1 virions at a ratio of approximately 1 molecul e of Vif for every 75 to 220 molecules of p24, or 7 to 20 molecules pe r virion. Furthermore, we demonstrate that the relative concentration of Vif is much lower in particles than in infected cells, whereas the opposite is observed for the main virus components. The viral envelope , Nef, Vpr, Vpu, protease, reverse transcriptase, integrase, nucleocap sid, and p6(gag) proteins as well as the viral genomic RNA, are dispen sable for Vif packaging. Furthermore, mutating several highly conserve d residues (H-108, C-114, C-133, L-145, and Q-146) or deleting the C-t erminal 18 amino acids of Vif, either of which severely impairs Vif fu nction, does not abolish its incorporation into virions. Finally, Vif can be packaged into murine leukemia virus particles. On the basis of these data, we conclude that the specificity of Vif incorporation into virions remains an open question.