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

J Virol. 2015 Dec;89(24):12518-24. doi: 10.1128/JVI.01838-15. Epub 2015 Sep 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 2 / genetics
  • Adaptor Protein Complex 2 / immunology
  • Adaptor Protein Complex 2 / metabolism*
  • CD4 Antigens / biosynthesis*
  • CD4 Antigens / genetics
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Down-Regulation*
  • Gene Knockdown Techniques
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / metabolism*
  • HIV Infections / pathology
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / metabolism*
  • Humans
  • nef Gene Products, Human Immunodeficiency Virus / genetics
  • nef Gene Products, Human Immunodeficiency Virus / immunology
  • nef Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Adaptor Protein Complex 2
  • CD4 Antigens
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1