AP-2 Is the Crucial Clathrin Adaptor Protein for CD4 Downmodulation by HIV-1 Nef in Infected Primary CD4+ T Cells

AP-2 Is the Crucial Clathrin Adaptor Protein for CD4 Downmodulation by HIV-1 Nef in Infected Primary CD4+ T Cells
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DOI:
10.1128/jvi.01838-15
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发表时间:
2015-12-01
影响因子:
5.4
通讯作者:
Schindler, Michael
Schindler, Michael
中科院分区:
医学2区
文献类型:
--
作者:
Gondim, Marcos Vinicius;Wiltzer-Bach, Linda;Schindler, Michael

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HIV-1 Nef介导的CD 4下调涉及多种宿主因素。我们研究了AP-1、AP-2、AP-3、V1 H-ATP酶、β-COP和ACOT 8在HIV-1感染的表达短发夹RNA(shRNA)的CD 4(+)T细胞中对CD 4下调的重要性,并通过福斯特共振能量转移(FRET)表征了与Nef的直接相互作用。慢病毒Nef与CD 4和AP-2的结合是保守的,并且仅AP-2敲低损害Nef介导的来自原代T细胞的CD 4下调。总之,在测试的因素中,AP-2是Nef介导的CD 4下调的最重要的参与者。
HIV-1 Nef-mediated CD4 downmodulation involves various host factors. We investigated the importance of AP-1, AP-2, AP-3, V1H-ATPase, beta-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 Forster 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.