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)-specific accessory protein that is required for the efficient release of viral particles from infected cells. Even though HIV-2 does not encode Vpu, we found that this virus is nevertheless capable of efficiently releasing 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 vpu+ HIV-1 NL4-3 isolate and was not further enhanced by expression of Vpu in trans. However, consistent with previous observations showing that HIV-2 particle release is Vpu responsive in the context of HIV-1/HIV-2 chimeric constructs; exchanging the gag-pol region of NL4-3 with the corresponding region from pROD10 rendered the resulting chimeric virus Vpu responsive. Our finding that the responsiveness of HIV-2 particle release to Vpu is context dependent suggested the presence of a Vpu-like factor(s) encoded by HIV-2. Using chimeric proviruses encoding HIV-2 gag and pol in the context of the HIV-1 provirus that were coexpressed with subgenomic HIV-2 constructs, we found that the HIV-2 envelope glycoprotein had the ability to enhance HIV-2 particle release with an efficiency comparable to that of the HIV-1 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 trans rescued the particle release defect of the ROD10 envelope mutant. Thus, unlike HIV-1, which encodes two separate proteins to regulate virus release or to mediate viral entry, the HIV-2 Env protein has evolved to perform both functions.
Bour
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Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
Schubert
U
U
Peden
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Strebel
K
K
D020126:Brefeldin A; D003517:Cyclopentanes / Q000494:pharmacology; D015693:Gene Products, nef / Q000378:metabolism; D016346:Gene Products, vif / Q000378:metabolism; D016336:Gene Products, vpr / Q000378:metabolism; D005814:Genes, Viral; D006023:Glycoproteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006679:HIV Seropositivity / Q000097:blood / Q000276:immunology; D015498:HIV-2 / Q000378:metabolism*; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D009154:Mutation; D014759:Viral Envelope Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000187:drug effects / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; D000086082:Viroporin Proteins
D020126:Brefeldin A; D003517:Cyclopentanes; D015693:Gene Products, nef; D016346:Gene Products, vif; D016336:Gene Products, vpr; D006023:Glycoproteins; D054298:Human Immunodeficiency Virus Proteins; D014759:Viral Envelope Proteins; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; C074286:VPX protein, Human immunodeficiency virus 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins