HIV-1 Env associates with HLA-C free-chains at the cell membrane modulating viral infectivity.
Author
Valenzuela Fernández, Agustín; Serena, Michela; Parolini, Francesca; Biswas, Priscilla; Sironi, Francesca; Blanco Miranda, Almudena; Zoratti, Elisa; Scupoli, Maria Teresa; Ziglio, Serena; Gibellini, Davide; Romanelli, Maria Grazia; Siccardi, Antonio; Malnati, Mauro; Beretta, Alberto; Zipeto, DonatoDate
2016Abstract
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 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.