Scientific article

HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes

Published inNature cell biology, vol. 2, no. 3, p. 163-167
Publication date2000

Major-histocompatibility-complex (MHC) proteins are used to display, on the surface of a cell, peptides derived from foreign material - such as a virus - that is infecting that cell. Cytotoxic T lymphocytes then recognize and kill the infected cell. The HIV-1 Nef protein downregulates the cell-surface expression of class I MHC proteins, and probably thereby promotes immune evasion by HIV-1. In the presence of Nef, class I MHC molecules are relocalized from the cell surface to the trans-Golgi network (TGN) through as-yet-unknown mechanisms. Here we show that Nef-induced downregulation of MHC-I expression and MHC-I targeting to the TGN require the binding of Nef to PACS-1, a molecule that controls the TGN localization of the cellular protein furin. This interaction is dependent on Nef's cluster of acidic amino acids. A chimaeric integral membrane protein containing Nef as its cytoplasmic domain localizes to the TGN after internalization, in an acidic-cluster- and PACS-1-dependent manner. These results support a model in which Nef relocalizes MHC-I by acting as a connector between MHC-I's cytoplasmic tail and the PACS-1-dependent protein-sorting pathway.

  • Animals
  • Antigens, CD4/metabolism
  • Capsid/antagonists & inhibitors/metabolism
  • Carrier Proteins
  • Cell Line
  • Down-Regulation/drug effects/physiology
  • Endocytosis/drug effects/genetics
  • Furin
  • Gene Expression Regulation/drug effects/genetics
  • Gene Products, nef/metabolism/pharmacology
  • Golgi Apparatus/metabolism
  • HIV-1/metabolism
  • Histocompatibility Antigens Class I/metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Melanoma/metabolism/pathology
  • Membrane Proteins/metabolism
  • Oligonucleotides, Antisense/pharmacology
  • Protein Structure, Tertiary/genetics
  • Rats
  • Receptor, IGF Type 2/metabolism
  • Recombinant Fusion Proteins/genetics/metabolism
  • Subtilisins/metabolism
  • Transfection
  • Vesicular Transport Proteins
  • Nef Gene Products, Human Immunodeficiency Virus
Citation (ISO format)
PIGUET, Vincent et al. HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes. In: Nature cell biology, 2000, vol. 2, n° 3, p. 163–167. doi: 10.1038/35004038
Main files (1)
Article (Published version)
ISSN of the journal1465-7392

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