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

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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Mohamed El-Far, Catherine Isabelle, Nicolas Chomont, Martin Bourbonnière, Simone Fonseca, et al.. Down-regulation of CTLA-4 by HIV-1 Nef protein.. PLoS ONE, Public Library of Science, 2013, 8 (1), pp.e54295. ⟨10.1371/journal.pone.0054295⟩. ⟨pasteur-01109470⟩

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