Journal
JOURNAL OF VIROLOGY
Volume 89, Issue 24, Pages 12518-12524Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01838-15
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Funding
- Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany
- Helmholtz Zentrum Munich, Neuherberg, Germany
- University Clinic Tuebingen, Tuebingen, Germany
- Deutsche Forschungsgemeinschaft (DFG)
- Brazilian agency Coordenacao de Aperfeicamento de Pessoal de Nivel Superior (CAPES)
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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.
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