Author:
Serena Michela,Parolini Francesca,Biswas Priscilla,Sironi Francesca,Blanco Miranda Almudena,Zoratti Elisa,Scupoli Maria Teresa,Ziglio Serena,Valenzuela-Fernandez Agustin,Gibellini Davide,Romanelli Maria Grazia,Siccardi Antonio,Malnati Mauro,Beretta Alberto,Zipeto Donato
Abstract
AbstractHLA-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 β2-microglobulin (β2m) 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 β2m, on the membrane of infected cells. The association between Env and HLA-C takes place at the cell membrane requiring β2m 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 β2m. HIV-1 Env-pseudotyped viruses produced in the absence of β2m are less infectious than those produced in the presence of β2m. We hypothesize that the conformation and surface expression of HLA-C molecules could be a discriminant for the association with Env. Binding stability to β2m 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.
Publisher
Springer Science and Business Media LLC
Cited by
16 articles.
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