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Down-regulation of CTLA-4 by HIV-1 Nef protein
Journal article   Open access   Peer reviewed

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

Mohamed El-Far, Catherine Isabelle, Nicolas Chomont, Martin Bourbonnière, Simone Fonseca, Petronela Ancuta, Yoav Peretz, Younes Chouikh, Rabih Halwani, Olivier Schwartz, …
PloS one, v 8(1), pp e54295-e54295
2013
PMID: 23372701
url
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0054295&type=printableView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1371/journal.pone.0054295View
Published, Version of Record (VoR) Open

Abstract

Amino Acid Motifs Antigens, CD4 CTLA-4 Antigen Down-Regulation Endocytosis Endosomes HEK293 Cells HeLa Cells HIV-1 Host-Pathogen Interactions Humans Life Sciences Lysosomes Microbiology and Parasitology nef Gene Products, Human Immunodeficiency Virus Recombinant Fusion Proteins Signal Transduction Transfection Virology
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.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
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