title: HIV-1 Env associates with HLA-C free-chains at the cell membrane modulating viral infectivity.
abstract: 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.
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Serena
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Parolini
authors.affiliation: IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Biswas
authors.affiliation: IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sironi
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.
authors.forename: Almudena
authors.initials: A
authors.lastname: Blanco Miranda
authors.affiliation: University Laboratory of Medical Research, Piazzale L. A. Scuro 10, 37134 Verona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Zoratti
authors.affiliation: University Laboratory of Medical Research, Piazzale L. A. Scuro 10, 37134 Verona, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Scupoli
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.|Laboratorio de Inmunología Celular y Viral, Unidad de Virología IUETSPC, Unidad de Farmacología, Sección de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna (ULL), Campus de Ofra s/n, 38071, Tenerife, Spain.
authors.forename: Serena
authors.initials: S
authors.lastname: Ziglio
authors.affiliation: Laboratorio de Inmunología Celular y Viral, Unidad de Virología IUETSPC, Unidad de Farmacología, Sección de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna (ULL), Campus de Ofra s/n, 38071, Tenerife, Spain.
authors.forename: Agustin
authors.initials: A
authors.lastname: Valenzuela-Fernandez
authors.affiliation: Department of Diagnostics and Public Health, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gibellini
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Romanelli
authors.affiliation: IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Siccardi
authors.affiliation: IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Malnati
authors.affiliation: IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Beretta
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Zipeto
mesh_terms: D002462:Cell Membrane / Q000821:virology*; D057809:HEK293 Cells; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development*; D015236:HLA-C Antigens / Q000378:metabolism*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D011485:Protein Binding; D001613:beta 2-Microglobulin / Q000378:metabolism*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D015236:HLA-C Antigens; D001613:beta 2-Microglobulin; D054299:env Gene Products, Human Immunodeficiency Virus