HIV-1 particle release mediated by Vpu is distinct from that mediated by p6

Vpu and the C-terminal peptide of Gag (p6) are both HIV-1-encoded proteins that augment the release of virus particles from cells. We examined the functional relationship between these proteins and their activities during particle release. Our results indicate that efficient HIV-1 particle release from HeLa and Jurkat cells depends on the presence of Vpu. However, Vpu is dispensable for efficient release from Cos cells. In contrast, p6 is required for efficient release from Cos cells but not from Jurkat or HeLa cells. These data suggest that Vpu and p6 have distinct activities in virus exit from different cell lines. Intracellular proteolytic processing of Gag precursor protein is more complete in Cos cells than in HeLa cells. However, this processing has little or no effect on Vpu- or p6-mediated particle release. p6 is required for incorporation of yet another virus protein (Vpr) into cells but our data suggest that Vpr plays no role in p6-dependent particle release. Vpu also facilitates the degradation of CD4 in virus producing cells but, in contrast to particle release, the ability of Vpu to facilitate the degradation of CD4 is not cell line-dependent.