title: AP-2 Is the Crucial Clathrin Adaptor Protein for CD4 Downmodulation by HIV-1 Nef in Infected Primary CD4+ T Cells.
abstract: HIV-1 Nef-mediated CD4 downmodulation involves various host factors. We investigated the importance of AP-1, AP-2, AP-3, V1H-ATPase, β-COP, and ACOT8 for CD4 downmodulation in HIV-1-infected short hairpin RNA (shRNA)-expressing CD4(+) T cells and characterized direct interaction with Nef by Förster resonance energy transfer (FRET). Binding of lentiviral Nefs to CD4 and AP-2 was conserved, and only AP-2 knockdown impaired Nef-mediated CD4 downmodulation from primary T cells. Altogether, among the factors tested, AP-2 is the most important player for Nef-mediated CD4 downmodulation.
authors.affiliation: Helmholtz Zentrum Munich, Institute of Virology, Neuherberg, Germany Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany Universidade de Brasília, Laboratório de Virologia Molecular Faculdade de Ciências da Saúde, Brasília, Brazil.
authors.forename: Marcos Vinicius
authors.initials: MV
authors.lastname: Gondim
authors.affiliation: Institute of Medical Virology, University Clinic Tübingen, Tübingen, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Wiltzer-Bach
authors.affiliation: Institute of Medical Virology, University Clinic Tübingen, Tübingen, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Maurer
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Banning
authors.affiliation: Universidade de Brasília, Laboratório de Virologia Molecular Faculdade de Ciências da Saúde, Brasília, Brazil.
authors.forename: Enrique
authors.initials: E
authors.lastname: Arganaraz
authors.affiliation: Helmholtz Zentrum Munich, Institute of Virology, Neuherberg, Germany Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany Institute of Medical Virology, University Clinic Tübingen, Tübingen, Germany michael.schindler@helmholtz-muenchen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Schindler
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D033962:Adaptor Protein Complex 2; D015704:CD4 Antigens; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1