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http://purl.uniprot.org/citations/29070683http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29070683http://www.w3.org/2000/01/rdf-schema#comment"HLA-C expression is associated with a differential ability to control HIV-1 infection. Higher HLA-C levels may lead to better control of HIV-1 infection through both a higher efficiency of antigen presentation to cytotoxic T lymphocytes and the triggering of activating killer immunoglobulin-like receptors on NK cells, whereas lower levels may provide poor HIV-1 control and rapid progression to AIDS. We characterized the relative amounts of HLA-C heterotrimers (heavy chain/β2 microglobulin [β2m]/peptide) and HLA-C free heavy chains on peripheral blood mononuclear cells (PBMCs) from healthy blood donors harboring both alleles with stable or unstable binding to β2m/peptide. We analyzed the stability of HLA-C heterotrimers of different allotypes and the infectivity of HIV-1 virions produced by PBMCs with various allotypes. We observed significant differences in HLA-C heterotrimer stability and in expression levels. We found that R5 HIV-1 virions produced by PBMCs harboring unstable HLA-C alleles were more infectious than those produced by PBMCs carrying the stable variants. We propose that HIV-1 infectivity might depend both on the amounts of HLA-C molecules and on their stability as trimeric complex. According to this model, individuals with low-expression HLA-C alleles and unstable binding to β2m/peptide might have worse control of HIV-1 infection and an intrinsically higher capacity to support viral replication.IMPORTANCE Following HIV-1 infection, some people advance rapidly to AIDS while others have slow disease progression. HLA-C, a molecule involved in immunity, is a key determinant of HIV-1 control. Here we reveal how HLA-C variants contribute to the modulation of viral infectivity. HLA-C is present on the cell surface in two different conformations. The immunologically active conformation is part of a complex that includes β2 microglobulin/peptide; the other conformation is not bound to β2 microglobulin/peptide and can associate with HIV-1, increasing its infectivity. Individuals with HLA-C variants with a predominance of immunologically active conformations would display stronger immunity to HIV-1, reduced viral infectivity and effective control of HIV-1 infection, while subjects with HLA-C variants that easily dissociate from β2 microglobulin/peptide would have a reduced immunological response to HIV-1 and produce more infectious virions. This study provides new information that could be useful in the design of novel vaccine strategies and therapeutic approaches to HIV-1."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.org/dc/terms/identifier"doi:10.1128/jvi.01711-17"xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Romanelli M.G."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Zipeto D."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Biswas P."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Beretta A."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Biassoni R."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Sironi F."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Ugolotti E."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Guizzardi E."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Malnati M."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Parolini F."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Serena M."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Scupoli M.T."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Gibellini D."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Cazzoletti L."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/author"Muraro V."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/name"J Virol"xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/pages"e01711-17"xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/title"Stability and Expression Levels of HLA-C on the Cell Membrane Modulate HIV-1 Infectivity."xsd:string
http://purl.uniprot.org/citations/29070683http://purl.uniprot.org/core/volume"92"xsd:string
http://purl.uniprot.org/citations/29070683http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29070683
http://purl.uniprot.org/citations/29070683http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/29070683
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