Journal article
Down-regulation of CTLA-4 by HIV-1 Nef protein
PloS one, v 8(1), pp e54295-e54295
2013
PMID: 23372701
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Down-regulation of CTLA-4 by HIV-1 Nef protein
- Creators
- Mohamed El-Far - Université de MontréalCatherine Isabelle - Université de MontréalNicolas Chomont - Université de MontréalMartin Bourbonnière - Université de MontréalSimone Fonseca - Université de MontréalPetronela Ancuta - Centre Hospitalier de l’Université de MontréalYoav Peretz - Université de MontréalYounes Chouikh - Université de MontréalRabih Halwani - King Saud UniversityOlivier Schwartz - Institut PasteurJoaquín Madrenas - McGill UniversityGordon J Freeman - Dana-Farber Cancer InstituteJean-Pierre Routy - McGill University Health CentreElias K Haddad - Hôpital Saint-LucRafick-Pierre Sékaly - Université de Montréal
- Publication Details
- PloS one, v 8(1), pp e54295-e54295
- Publisher
- Public Library of Science
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000314021500053
- Scopus ID
- 2-s2.0-84872804428
- Other Identifier
- 991020099991304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology