Down-regulation of CTLA-4 by HIV-1 Nef Protein

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Feb 2

PMID 23372701

Citations 14

Authors

Mohamed El-Far

Catherine Isabelle

Nicolas Chomont

Martin Bourbonniere

Simone Fonseca

Petronela Ancuta

Yoav Peretz

Younes Chouikh

Rabih Halwani

Olivier Schwartz

Joaquin Madrenas

Gordon J Freeman

Jean-Pierre Routy

Elias K Haddad

Rafick-Pierre Sekaly

Affiliations

Soon will be listed here.

Abstract

HIV-1 Nef protein down-regulates several cell surface receptors through its interference with the cell sorting and trafficking machinery. Here we demonstrate for the first time the ability of Nef to down-regulate cell surface expression of the negative immune modulator CTLA-4. Down-regulation of CTLA-4 required the Nef motifs DD175, EE155 and LL165, all known to be involved in vesicle trafficking. Disruption of the lysosomal functions by pH-neutralizing agents prevented CTLA-4 down-regulation by Nef, demonstrating the implication of the endosomal/lysosomal compartments in this process. Confocal microscopy experiments visualized the co-localization between Nef and CTLA-4 in the early and recycling endosomes but not at the cell surface. Overall, our results provide a novel mechanism by which HIV-1 Nef interferes with the surface expression of the negative regulator of T cell activation CTLA-4. Down-regulation of CTLA-4 may contribute to the mechanisms by which HIV-1 sustains T cell activation, a critical step in viral replication and dissemination.

Citing Articles

Unequal distribution of genetically-intact HIV-1 proviruses in cells expressing the immune checkpoint markers PD-1 and/or CTLA-4.

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Concanamycin A counteracts HIV-1 Nef to enhance immune clearance of infected primary cells by cytotoxic T lymphocytes.

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