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2.
Sci Rep ; 7: 40037, 2017 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-28051183

RESUMEN

HLA-C has been demonstrated to associate with HIV-1 envelope glycoprotein (Env). Virions lacking HLA-C have reduced infectivity and increased susceptibility to neutralizing antibodies. Like all others MHC-I molecules, HLA-C requires ß2-microglobulin (ß2m) for appropriate folding and expression on the cell membrane but this association is weaker, thus generating HLA-C free-chains on the cell surface. In this study, we deepen the understanding of HLA-C and Env association by showing that HIV-1 specifically increases the amount of HLA-C free chains, not bound to ß2m, on the membrane of infected cells. The association between Env and HLA-C takes place at the cell membrane requiring ß2m to occur. We report that the enhanced infectivity conferred to HIV-1 by HLA-C specifically involves HLA-C free chain molecules that have been correctly assembled with ß2m. HIV-1 Env-pseudotyped viruses produced in the absence of ß2m are less infectious than those produced in the presence of ß2m. We hypothesize that the conformation and surface expression of HLA-C molecules could be a discriminant for the association with Env. Binding stability to ß2m may confer to HLA-C the ability to preferentially act either as a conventional immune-competent molecule or as an accessory molecule involved in HIV-1 infectivity.


Asunto(s)
Membrana Celular/virología , Infecciones por VIH/virología , VIH-1/crecimiento & desarrollo , Antígenos HLA-C/metabolismo , Interacciones Huésped-Patógeno , Microglobulina beta-2/metabolismo , Productos del Gen env del Virus de la Inmunodeficiencia Humana/metabolismo , Células HEK293 , Células HeLa , Humanos , Unión Proteica
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