Article abstract
Nature Cell Biology 2, 163 - 167 (2000)
Published online: 9 February 2000 | doi:10.1038/35004038
HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes
Vincent Piguet1,2, Lei Wan3, Christelle Borel1, Aram Mangasarian1, Nicolas Demaurex4, Gary Thomas3 & Didier Trono1
Abstract
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.
- Department of Genetics and Microbiology, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland
- Department of Dermatology, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland
- Vollum Institute, The Oregon Health Sciences University, Portland, Oregon 97201, USA
- Department of Physiology, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland
Correspondence to: Gary Thomas3 e-mail: thomasg@ohsu.edu
Correspondence to: Didier Trono1 e-mail: didier.trono@medecine.unige.ch
