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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Down-Regulation of CTLA-4 by HIV-1 Nef Protein
PLoS ONE, Volume 8, No. 1, Article e54295, Year 2013
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Description
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. © 2013 El-Far et al.
Authors & Co-Authors
El-Far, Mohamed
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Canada, Ontario
Boehringer Ingelheim Canada Ltd.
Isabelle, Catherine
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Chomont, Nicolas
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
United States, Miami
Vaccine and Gene Therapy Institute of Florida
Bourbonnière, Martin
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Fonseca, Simone Gonçalves
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
United States, Miami
Vaccine and Gene Therapy Institute of Florida
Brazil, Goiania
Universidade Federal de Goiás
Ancuta, Petronela
Canada, Montreal
Hopital Saint-luc
Peretz, Yoav
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Chouikh, Younes
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
Halwani, Rabih
Saudi Arabia, Riyadh
College of Medicine
Schwartz, Olivier
France, Paris
Institut Pasteur, Paris
Madrenas, Joaquín
Canada, Montreal
Université Mcgill
Freeman, Gordon James
United States, Boston
Harvard Medical School
Routy, Jean Pierre G.
Canada, Montreal
Mcgill University Health Centre, Royal Victoria Hospital
Haddad, Elias K.
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
United States, Miami
Vaccine and Gene Therapy Institute of Florida
Seḱaly, Rafick Pierre
Canada, Montreal
Hopital Saint-luc
Canada, Montreal
University of Montreal
United States, Miami
Vaccine and Gene Therapy Institute of Florida
Statistics
Citations: 29
Authors: 15
Affiliations: 10
Identifiers
Doi:
10.1371/journal.pone.0054295
e-ISSN:
19326203
Research Areas
Infectious Diseases