title: Genetic and phenotypic analyses of sequential vpu alleles from HIV-infected IFN-treated patients.
abstract: Treatment of HIV-infected patients with IFN-α results in significant, but clinically insufficient, reductions of viremia. IFN induces the expression of several antiviral proteins including BST-2, which inhibits HIV by multiple mechanisms. The viral protein Vpu counteracts different effects of BST-2. We thus asked if Vpu proteins from IFN-treated patients displayed improved anti-BST-2 activities as compared to Vpu from baseline. Deep-sequencing analyses revealed that in five of seven patients treated by IFN-α for a concomitant HCV infection in the absence of antiretroviral drugs, the dominant Vpu sequences differed before and during treatment. In three patients, vpu alleles that emerged during treatment improved virus replication in the presence of IFN-α, and two of them conferred improved virus budding from cells expressing BST-2. Differences were observed for the ability to down-regulate CD4, while all Vpu variants potently down-modulated BST-2 from the cell surface. This report discloses relevant consequences of IFN-treatment on HIV properties.
authors.affiliation: INSERM, U941, Paris F-75010, France; Univ Paris Diderot, Sorbonne Paris Cité, F-75475 Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Vanwalscappel
authors.affiliation: INSERM, U941, Paris F-75010, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rato
authors.affiliation: AIDS Immunopathogenesis Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Mayte
authors.initials: M
authors.lastname: Perez-Olmeda
authors.affiliation: AIDS Immunopathogenesis Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Díez Fuertes
authors.affiliation: Virus & Immunity Unit, Institut Pasteur, CNRS-URA 3015, Paris, France.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Casartelli
authors.affiliation: AIDS Immunopathogenesis Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: JA.ppalcami@isciii.es.
authors.forename: José
authors.initials: J
authors.lastname: Alcami
authors.affiliation: INSERM, U941, Paris F-75010, France; Univ Paris Diderot, Sorbonne Paris Cité, F-75475 Paris, France. Electronic address: FM.fabrizio.mammano@inserm.fr.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mammano
mesh_terms: D000483:Alleles; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D010641:Phenotype; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000378:metabolism; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D016898:Interferon-alpha; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
keywords: BST-2; Evolution; HIV-1; Interferon; Restriction factor; Vpu