Stability and Expression Levels of HLA-C on the Cell Membrane Modulate HIV-1 Infectivity

• DOI: 10.1128/jvi.01711-17
• Publication Date: 2017-10-25T21:30:09Z
• Authors: Francesca Parolini; Priscilla Biswas; Michela Serena; Francesca Sironi; Valentina Muraro; Elisabetta Guizzardi; Lucia Cazzoletti; Maria Teresa Scupoli; Davide Gibellini; Elisabetta Ugolotti; Roberto Biassoni; Alberto Beretta; Mauro Malnati; Maria Grazia Roma...; Donato Zipeto
• Keywords: Infectivity; HLA-B Antigens

HLA-C expression is associated with a differential ability to control HIV-1 infection. Higher levels may lead better of infection through both higher efficiency antigen presentation cytotoxic T lymphocytes and the triggering activating killer immunoglobulin-like receptors on NK cells, whereas lower provide poor rapid progression AIDS. We characterized relative amounts heterotrimers (heavy chain/β2 microglobulin [β2m]/peptide) free heavy chains peripheral blood mononuclear cells (PBMCs) from healthy donors harboring alleles stable or unstable binding β2m/peptide. analyzed stability different allotypes infectivity virions produced by PBMCs various allotypes. observed significant differences in heterotrimer levels. found that R5 were more infectious than those carrying variants. propose might depend molecules their as trimeric complex. According this model, individuals low-expression β2m/peptide have worse an intrinsically capacity support viral replication.IMPORTANCE Following infection, some people advance rapidly AIDS while others slow disease progression. HLA-C, molecule involved immunity, key determinant control. Here we reveal how variants contribute modulation infectivity. present cell surface two conformations. The immunologically active conformation part complex includes β2 microglobulin/peptide; other not bound microglobulin/peptide can associate HIV-1, increasing its Individuals predominance conformations would display stronger immunity reduced effective subjects easily dissociate immunological response produce virions. This study provides new information could be useful design novel vaccine strategies therapeutic approaches HIV-1.