{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T07:49:35Z","timestamp":1767167375810,"version":"build-2238731810"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2017,12,14]],"date-time":"2017-12-14T00:00:00Z","timestamp":1513209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    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\/\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    microglobulin [\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m]\/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 \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\/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 \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\/peptide might have worse control of HIV-1 infection and an intrinsically higher capacity to support viral replication.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    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 \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    microglobulin\/peptide; the other conformation is not bound to \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    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 \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    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.\n                  <\/jats:p>","DOI":"10.1128\/jvi.01711-17","type":"journal-article","created":{"date-parts":[[2017,10,25]],"date-time":"2017-10-25T17:30:09Z","timestamp":1508952609000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Stability and Expression Levels of HLA-C on the Cell Membrane Modulate HIV-1 Infectivity"],"prefix":"10.1128","volume":"92","author":[{"given":"Francesca","family":"Parolini","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscilla","family":"Biswas","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Serena","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Sironi","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Muraro","sequence":"additional","affiliation":[{"name":"Service of Transfusion Medicine, AOUI, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Guizzardi","sequence":"additional","affiliation":[{"name":"Service of Transfusion Medicine, AOUI, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Cazzoletti","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Public Health, University of Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Scupoli","sequence":"additional","affiliation":[{"name":"University Laboratory of Medical Research, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Gibellini","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Public Health, University of Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Ugolotti","sequence":"additional","affiliation":[{"name":"IRCCS Institute Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Biassoni","sequence":"additional","affiliation":[{"name":"IRCCS Institute Giannina Gaslini, Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Beretta","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Malnati","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Grazia","family":"Romanelli","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2168-4144","authenticated-orcid":false,"given":"Donato","family":"Zipeto","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1143767"},{"key":"e_1_3_2_3_2","first-page":"127","article-title":"The ins and outs of intracellular peptides and antigen presentation by MHC class I molecules","volume":"300","author":"Groothuis T","year":"2005","unstructured":"Groothuis T, Neefjes J. 2005. 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