HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-2 ENVELOPE PROTEIN IS A FUNCTIONAL COMPLEMENT TO HIV TYPE-1 VPU THAT ENHANCES PARTICLE RELEASE OF HETEROLOGOUS RETROVIRUSES

We have recently shown that the envelope glycoprotein of the ROD10 iso late of human immunodeficiency virus type 2 (HIV-2) has the ability to positively regulate HIV-2 viral particle release, The activity provid ed by the ROD10 Env was remarkably similar to that of the HIV-1 Vpu pr otein, thus raising the possibility that the two proteins act in a rel ated fashion, We now show that the ROD10 Env can functionally replace Vpu to enhance the rate of HIV-1 particle release. When provided in tr ans, both Vpu and the ROD10 Env restored wild-type levels of particle release in a Vpu-deficient mutant of the NL4-3 molecular clone with in distinguishable efficiencies. This effect was independent of the prese nce of the HIV-1 envelope protein. The ROD10 Env also enhanced HIV-1 p article release in the context of HIV-2 chimeric viruses containing th e HIV-1 gag-pol, indicating a lack of need for additional HIV-1 produc ts in this process, In addition, we show for the first time that HIV-1 Vpu, as well as ROD10 Env, has the ability to enhance simian immunode ficiency virus (SIV) particle release. The effects of Vpu and ROD10 En v on SIV particle release were indistinguishable and were observed in the context of full-length SIV mac239 and simian-human immunodeficienc y virus chimeras, These results further demonstrate that ROD10 Env can functionally complement Vpu with respect to virus release, In contras t, we found no evidence of a destabilizing activity of ROD10 Env on th e CD4 molecule, HIV-1 and HIV-2 thus appear to have evolved geneticall y distinct but functionally similar strategies to resolve the common p roblem of efficient release of progeny virus from infected cells.