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The HIV-1 Nef protein acts as a connector with sorting pathways in the Golgi and at the plasma membrane

A Mangasarian1, M Foti, C Aiken

  • 1Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.

Immunity
|January 1, 1997
PubMed

Insights

The HIV Nef protein targets CD4 and MHC I for removal from cell surfaces by hijacking cellular transport pathways. This mechanism involves accelerated endocytosis, leading to reduced receptor expression.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • The Human Immunodeficiency Virus (HIV) Nef protein is known to down-regulate cell surface expression of CD4 and MHC I.
  • This down-regulation is partly mediated by accelerated endocytosis of these receptors.

Purpose of the Study:

  • To elucidate the precise mechanism by which HIV Nef protein mediates the down-regulation of CD4 and MHC I.
  • To investigate the role of Nef's cytoplasmic domain in receptor trafficking and internalization.

Main Methods:

  • Creation of chimeric integral membrane proteins fusing extracellular/transmembrane regions of CD4 or CD8 with the Nef cytoplasmic domain.
  • Analysis of the ability of these chimeras to down-modulate CD4 in trans.
  • Investigation of the endocytosis pathways and Golgi localization of Nef-containing chimeras.

Main Results:

  • Fusion molecules with Nef cytoplasmic domains could down-modulate CD4 in a dileucine-dependent manner.
  • Nef-containing chimeras, despite lacking intrinsic internalization signals, exhibited Golgi retention and rapid endocytosis via clathrin-coated pits.
  • These findings indicate Nef's direct involvement in receptor sorting pathways.

Conclusions:

  • HIV Nef protein likely down-regulates CD4 and MHC I by physically linking these receptors to cellular sorting machinery.
  • Nef acts at both the Golgi and plasma membrane to facilitate receptor internalization and reduce cell surface expression.
  • This mechanism highlights a critical viral strategy for immune evasion.

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