HIV-1 Nef blocks transport of MHC class I molecules to the cell surface via a PI 3-kinase-dependent pathway

Virology. 2001 Apr 10;282(2):267-77. doi: 10.1006/viro.2000.0816.

Abstract

HIV causes a chronic infection by evading immune eradication. A key element of HIV immune escape is the HIV-1 Nef protein. Nef causes a reduction in the level of cell surface major histocompatibility complex class I (MHC-I) protein expression, thus protecting HIV-infected cells from anti-HIV cytotoxic T lymphocyte (CTL) recognition and killing. Nef also reduces cell surface levels of the HIV receptor, CD4, by accelerating endocytosis. We show here that endocytosis is not required for Nef-mediated downmodulation of MHC-I molecules. The main effect of Nef is to block transport of MHC-I molecules to the cell surface, leading to accumulation in intracellular organelles. Furthermore, the effect of Nef on MHC-I molecules (but not on CD4) requires phosphoinositide 3-kinase (PI 3-kinase) activity. We propose that Nef diverts MHC-1 proteins into a PI 3-kinase-dependent transport pathway that prevents expression on the cell surface.

Publication types

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

MeSH terms

  • Blotting, Western
  • CD4 Antigens / metabolism
  • Cell Membrane / metabolism*
  • Chromones / pharmacology
  • Down-Regulation
  • Dynamins
  • Endocytosis
  • Flow Cytometry
  • GTP Phosphohydrolases / metabolism
  • Gene Products, nef / chemistry
  • Gene Products, nef / metabolism*
  • Golgi Apparatus / chemistry
  • Golgi Apparatus / metabolism
  • HIV-1 / physiology*
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / metabolism*
  • Humans
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Transport
  • Recombinant Fusion Proteins / metabolism
  • Tumor Cells, Cultured
  • nef Gene Products, Human Immunodeficiency Virus
  • src Homology Domains

Substances

  • CD4 Antigens
  • Chromones
  • Gene Products, nef
  • HLA-A2 Antigen
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Recombinant Fusion Proteins
  • nef Gene Products, Human Immunodeficiency Virus
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • GTP Phosphohydrolases
  • Dynamins