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Journal articles
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.
Cited literature [63 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-01109470
Contributor : Isma Ziani <>
Submitted on : Monday, January 26, 2015 - 1:56:21 PM
Last modification on : Monday, August 31, 2020 - 4:24:56 PM
Long-term archiving on: : Friday, September 11, 2015 - 9:20:57 AM
Contributor : Isma Ziani <>
Submitted on : Monday, January 26, 2015 - 1:56:21 PM
Last modification on : Monday, August 31, 2020 - 4:24:56 PM
Long-term archiving on: : Friday, September 11, 2015 - 9:20:57 AM
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journal.pone.0054295.pdf
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