HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail

J Cell Biol. 2004 Dec 6;167(5):903-13. doi: 10.1083/jcb.200407031. Epub 2004 Nov 29.

Abstract

To avoid immune recognition by cytotoxic T lymphocytes (CTLs), human immunodeficiency virus (HIV)-1 Nef disrupts the transport of major histocompatibility complex class I molecules (MHC-I) to the cell surface in HIV-infected T cells. However, the mechanism by which Nef does this is unknown. We report that Nef disrupts MHC-I trafficking by rerouting newly synthesized MHC-I from the trans-Golgi network (TGN) to lysosomal compartments for degradation. The ability of Nef to target MHC-I from the TGN to lysosomes is dependent on expression of the mu1 subunit of adaptor protein (AP) AP-1A, a cellular protein complex implicated in TGN to endolysosomal pathways. We demonstrate that in HIV-infected primary T cells, Nef promotes a physical interaction between endogenous AP-1 and MHC-I. Moreover, we present data that this interaction uses a novel AP-1 binding site that requires amino acids in the MHC-I cytoplasmic tail. In sum, our evidence suggests that binding of AP-1 to the Nef-MHC-I complex is an important step required for inhibition of antigen presentation by HIV.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Protein Complex 1 / metabolism*
  • Adaptor Protein Complex mu Subunits / metabolism
  • Antigen Presentation / immunology
  • Binding Sites / immunology
  • Cell Line
  • Cell Membrane / immunology
  • Cell Membrane / virology
  • Cytoplasm / immunology
  • Cytoplasm / virology
  • Gene Products, nef / immunology
  • Gene Products, nef / metabolism*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Lysosomes / metabolism
  • Lysosomes / virology
  • Models, Biological
  • Protein Structure, Tertiary / physiology
  • Protein Transport / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology*
  • nef Gene Products, Human Immunodeficiency Virus
  • trans-Golgi Network / metabolism
  • trans-Golgi Network / virology

Substances

  • Adaptor Protein Complex 1
  • Adaptor Protein Complex mu Subunits
  • Gene Products, nef
  • Histocompatibility Antigens Class I
  • nef Gene Products, Human Immunodeficiency Virus