THE ENVELOPE GLYCOPROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 ENHANCES VIRAL PARTICLE RELEASE - A VPU-LIKE FACTOR

The Vpu protein is a human immunodeficiency virus type 1 (HIV-1)-speci fic accessory protein that is required for the efficient release of vi ral particles from infected cells, Even though HIV-2 does not encode V pu, we found that this virus is nevertheless capable of efficiently re leasing virus particles. In fact, the rate of virus release from HeLa cells transfected with a full-length molecular clone of HIV-2, ROD10, was comparable to that observed for the vpr(+) HIV-1 NL4-3 isolate and was not further enhanced by expression of Vpu in trans. However, cons istent with previous observations showing that HIV-2 particle release is Vpu responsive in the context of HIV-1/HIV-2 chimeric constructs, e xchanging the gag-pol region of NL4-3 with the corresponding region fr om pROD10 rendered the resulting chimeric virus Vpu responsive, Our fi nding that the responsiveness of HIV-2 particle release to Vpu is cont ext dependent suggested the presence of a Vpu-like factor(s) encoded b y HIV-2. Using chimeric proviruses encoding HIV-2 gag and pol in the c ontext of the HIV-1 provirus that were coexpressed with subgenomic HIV -2 constructs, we found that the HIV-2 envelope glycoprotein had the a bility to enhance HIV-2 particle release with an efficiency comparable to that of the HIV-I Vpu protein, Conversely, inactivation of the HIV -2 env gene in the original ROD10 clone resulted in a decrease in the rate of viral particle release to a level that was comparable to that of Vpu-deficient HIV-1 isolates. Providing the wild-type envelope in t rans rescued the particle release defect of the ROD10 envelope mutant, Thus, unlike HIV-1, which encodes two separate proteins to regulate v irus release or to mediate viral entry, the HIV-2 Env protein has evol ved to perform both functions.