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Updated: Aug 8, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners
14:28

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: July 1, 2013

Nef interacts with the mu subunit of clathrin adaptor complexes and reveals a cryptic sorting signal in MHC I

S Le Gall1, L Erdtmann, S Benichou

  • 1Laboratoire Rétrovirus et Transfert Génétique Unité de Recherche Associée CNRS 1157, Institut Pasteur, Paris, France.

Immunity
|May 20, 1998
PubMed

Insights

The HIV Nef protein causes reduced surface expression of MHC I by altering HLA-A and -B molecule sorting. Nef enables a cryptic sorting signal, leading to MHC I accumulation in the Golgi.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Human Immunodeficiency Virus (HIV) infection leads to decreased surface expression of Major Histocompatibility Complex I (MHC I) molecules.
  • MHC I downregulation is a key mechanism employed by viruses to evade host immune responses.

Purpose of the Study:

  • To investigate the role of the HIV Nef protein in the intracellular trafficking of MHC I molecules, specifically HLA-A and -B.
  • To elucidate the mechanism by which Nef modulates MHC I surface expression.

Main Methods:

  • Immunofluorescence microscopy to observe the localization of HLA-A and -B in the presence and absence of Nef.
  • Analysis of protein-protein interactions between Nef and components of the cellular sorting machinery.

Main Results:

  • HIV Nef protein causes HLA-A and -B molecules to accumulate in the Golgi apparatus.
  • Nef facilitates the colocalization of MHC I with clathrin-coated vesicles.
  • A tyrosine-based sorting signal in the cytoplasmic tail of HLA-A and -B heavy chains is essential for Nef-mediated modulation.
  • Nef interacts with the mu subunit of AP adaptor complexes, linking MHC I to the clathrin-dependent sorting pathway.

Conclusions:

  • The HIV Nef protein actively disrupts normal MHC I trafficking.
  • Nef hijacks the cellular sorting machinery via interaction with AP complexes to internalize MHC I.
  • This Nef-mediated downregulation of MHC I contributes to immune evasion during HIV infection.

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