Vpu and the C-terminal peptide of Gag (p6) are both HIV-1-encoded prot
eins that augment the release of virus particles from cells. We examin
ed the functional relationship between these proteins and their activi
ties 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 cel
ls. In contrast, p6 is required for efficient release from Cos cells b
ut not from Jurkat or HeLa cells. These data suggest that Vpu and p6 h
ave distinct activities in virus exit from different cell lines. Intra
cellular proteolytic processing of Gag precursor protein is more compl
ete in Cos cells than in HeLa cells. However, this processing has litt
le or no effect on Vpu- or p6-mediated particle release. p6 is require
d for incorporation of yet another virus protein (Vpr) into cells but
our data suggest that Vpr plays no role in p6-dependent particle relea
se; Vpu also facilitates the degradation of CD4 in virus producing cel
ls but, in contrast to particle release, the ability of Vpu to facilit
ate the degradation of CD4 is not cell line-dependent. (C) 1996 Academ
ic Press, Inc.