Down-regulation of CTLA-4 by HIV-1 nef protein
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2013-01
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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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EL-FAR, Mohamed; ISABELLE, Catherine; CHOMONT, Nicolas; BOURBONNIÈRE, Martin; FONSECA, Simone; ANCUTA, Petronela; PERETZ, Yoav; CHOUIKH,Younes; HALWANI, Rabih; SCHWARTZ, Olivier; MADRENAS, Joaquín; FREEMAN, Gordon J.; ROUTY, Jean-Pierre; HADDAD, Elias K.; SÉKALY, Rafick-Pierre. Down-regulation of CTLA-4 by HIV-1 nef protein. Plos One, San Francisco, v. 8, n. 1, p. e54295, Jan. 2013.