title: The human immunodeficiency virus (HIV) type 2 envelope protein is a functional complement to HIV type 1 Vpu that enhances particle release of heterologous retroviruses.
abstract: We have recently shown that the envelope glycoprotein of the ROD10 isolate of human immunodeficiency virus type 2 (HIV-2) has the ability to positively regulate HIV-2 viral particle release. The activity provided by the ROD10 Env was remarkably similar to that of the HIV-1 Vpu protein, thus raising the possibility that the two proteins act in a related fashion. We now show that the ROD10 Env can functionally replace Vpu to enhance the rate of HIV-1 particle release. When provided in trans, 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 indistinguishable efficiencies. This effect was independent of the presence of the HIV-1 envelope protein. The ROD10 Env also enhanced HIV-1 particle release in the context of HIV-2 chimeric viruses containing the HIV-1 gag-pol, indicating a lack of need for additional HIV-1 products 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 immunodeficiency virus (SIV) particle release. The effects of Vpu and ROD10 Env on SIV particle release were indistinguishable and were observed in the context of full-length SIVmac239 and simian-human immunodeficiency virus chimeras. These results further demonstrate that ROD10 Env can functionally complement Vpu with respect to virus release. In contrast, we found no evidence of a destabilizing activity of ROD10 Env on the CD4 molecule. HIV-1 and HIV-2 thus appear to have evolved genetically distinct but functionally similar strategies to resolve the common problem of efficient release of progeny virus from infected cells.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0460, USA. sb32i@nih.gov
authors.forename: S
authors.initials: S
authors.lastname: Bour
authors.forename: K
authors.initials: K
authors.lastname: Strebel
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D015967:Gene Expression Regulation, Viral; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015498:HIV-2 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits; D016865:Reassortant Viruses / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly; D054299:env Gene Products, Human Immunodeficiency Virus; D000086082:Viroporin Proteins
chemical_list: D015704:CD4 Antigens; D015686:Gene Products, env; D054298:Human Immunodeficiency Virus Proteins; D011498:Protein Precursors; D054334:Viral Regulatory and Accessory Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C066315:gp140 envelope protein, Human immunodeficiency virus 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins