HIV-1 viral protein U (Vpu) facilitates virus particle release. To det
ermine whether Gag is sufficient for generation of a target for Vpu-me
diated particle release, we expressed HIV-1 Gag protein in the absence
of the other viral genes. The resulting particles were still Vpu resp
onsive. Mutational analysis of Gag indicated that the matrix domain (M
A) is required for Vpu responsiveness. However, additional mutations i
n other domains of Ga, which affect the formation of stable virus part
icles, also abrogate Vpu responsiveness on total Gag release. Coexpres
sion of the wild-type gag gene-and a gag mutant lacking the MA domain
renders the MA(-) mutant Vpu responsive. This indicates that Gag molec
ules lacking MA are still incorporated into particles through associat
ion with wild-type Gag molecules and that the resulting composite part
icles are sufficient for Vpu-mediated exit. (C) 1997 Academic Press.