The HIV-1 matrix domain of Gag is required for Vpu responsiveness during particle release.

HIV-1 viral protein U (Vpu) facilitates virus particle release. To determine whether Gag is sufficient for generation of a target for Vpu-mediated particle release, we expressed HIV-1 Gag protein in the absence of the other viral genes. The resulting particles were still Vpu responsive. Mutational analysis of Gag indicated that the matrix domain (MA) is required for Vpu responsiveness. However, additional mutations in other domains of Gag, which affect the formation of stable virus particles, also abrogate Vpu responsiveness on total Gag release. Coexpression of the wild-type gag gene and a gag mutant lacking the MA domain renders the MA- mutant Vpu responsive. This indicates that Gag molecules lacking MA are still incorporated into particles through association with wild-type Gag molecules and that the resulting composite particles are sufficient for Vpu-mediated exit.