Gondim Marcos Vinicius, Wiltzer-Bach Linda, Maurer Brigitte, Banning Carina, Arganaraz Enrique, Schindler Michael
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.
Institute of Medical Virology, University Clinic Tübingen, Tübingen, Germany.
J Virol. 2015 Dec;89(24):12518-24. doi: 10.1128/JVI.01838-15. Epub 2015 Sep 30.
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.
HIV-1 Nef介导的CD4下调涉及多种宿主因子。我们研究了AP-1、AP-2、AP-3、V1H-ATP酶、β-COP和ACOT8对HIV-1感染的表达短发夹RNA(shRNA)的CD4(+) T细胞中CD4下调的重要性,并通过荧光共振能量转移(FRET)表征了它们与Nef的直接相互作用。慢病毒Nefs与CD4和AP-2的结合是保守的,只有敲低AP-2会损害原代T细胞中Nef介导的CD4下调。总之,在所测试的因子中,AP-2是Nef介导的CD4下调中最重要的因子。