{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:04Z","timestamp":1790035204978,"version":"4.0.1"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2018,4,10]],"date-time":"2018-04-10T00:00:00Z","timestamp":1523318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T00:00:00Z","timestamp":1525219200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF 2010-17226"],"award-info":[{"award-number":["SAF 2010-17226"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF 2016-77894-R"],"award-info":[{"award-number":["SAF 2016-77894-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["FIS PI 13\/02269"],"award-info":[{"award-number":["FIS PI 13\/02269"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["RIS-RETIC grant RD12\/0017\/0036"],"award-info":[{"award-number":["RIS-RETIC grant RD12\/0017\/0036"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["RD12\/0016\/0028"],"award-info":[{"award-number":["RD12\/0016\/0028"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["BIO29 UNLL10-3E-783"],"award-info":[{"award-number":["BIO29 UNLL10-3E-783"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2015-64118-R"],"award-info":[{"award-number":["SAF2015-64118-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["RIS-RETIC grant RD16\/0025\/0011"],"award-info":[{"award-number":["RIS-RETIC grant RD16\/0025\/0011"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["RIS-RETIC RD12\/0017\/0034"],"award-info":[{"award-number":["RIS-RETIC RD12\/0017\/0034"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["FIS PI14\/01307"],"award-info":[{"award-number":["FIS PI14\/01307"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["PI17\/01518"],"award-info":[{"award-number":["PI17\/01518"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["RD12\/0017\/0002"],"award-info":[{"award-number":["RD12\/0017\/0002"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["RD16\/0025\/0041"],"award-info":[{"award-number":["RD16\/0025\/0041"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["No. OT\/14\/115"],"award-info":[{"award-number":["No. OT\/14\/115"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G066215N"],"award-info":[{"award-number":["G066215N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2018,5,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A small group of HIV-1-infected individuals, called long-term nonprogressors (LTNPs), and in particular a subgroup of LTNPs, elite controllers (LTNP-ECs), display permanent control of viral replication and lack of clinical progression. This control is the result of a complex interaction of host, immune, and viral factors. We identified, by phylogenetic analysis, a cluster of LTNP-ECs infected with very similar low-replication HIV-1 viruses, suggesting the contribution of common viral features to the clinical LTNP-EC phenotype. HIV-1 envelope (Env) glycoprotein mediates signaling and promotes HIV-1 fusion, entry, and infection, being a key factor of viral fitness\n                    <jats:italic>in vitro<\/jats:italic>\n                    , cytopathicity, and infection progression\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Therefore, we isolated full-length\n                    <jats:italic>env<\/jats:italic>\n                    genes from viruses of these patients and from chronically infected control individuals. Functional characterization of the initial events of the viral infection showed that Envs from the LTNP-ECs were ineffective in the binding to CD4 and in the key triggering of actin\/tubulin-cytoskeleton modifications compared to Envs from chronic patients. The viral properties of the cluster viruses result in a defective viral fusion, entry, and infection, and these properties were inherited by every virus of the cluster. Therefore, inefficient HIV-1 Env functions and signaling defects may contribute to the low viral replication capacity and transmissibility of the cluster viruses, suggesting a direct role in the LTNP-EC phenotype of these individuals. These results highlight the important role of viral characteristics in the LTNP-EC clinical phenotype. These Env viral properties were common to all the cluster viruses and thus support the heritability of the viral characteristics.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    HIV-1 long-term nonprogressor elite controller patients, due to their permanent control of viral replication, have been the object of numerous studies to identify the factors responsible for this clinical phenotype. In this work, we analyzed the viral characteristics of the envelopes of viruses from a phylogenetic cluster of LTNP-EC patients. These envelopes showed ineffective binding to CD4 and the subsequent signaling activity to modify actin\/tubulin cytoskeletons, which result in low fusion and deficient entry and infection capacities. These Env viral characteristics could explain the nonprogressor clinical phenotype of these patients. In addition, these inefficient\n                    <jats:italic>env<\/jats:italic>\n                    viral properties were present in all viruses of the cluster, supporting the heritability of the viral phenotype.\n                  <\/jats:p>","DOI":"10.1128\/mbio.02338-17","type":"journal-article","created":{"date-parts":[[2018,4,9]],"date-time":"2018-04-09T07:10:11Z","timestamp":1523257811000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":51,"title":["Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers"],"prefix":"10.1128","volume":"9","author":[{"given":"Concepci\u00f3n","family":"Casado","sequence":"first","affiliation":[{"name":"Unidad de Virologia Molecular, Laboratorio de Referencia e Investigaci\u00f3n en Retrovirus, Centro Nacional de Microbiolog\u00eda (CNM), Instituto de Salud Carlos IIII, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Marrero-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Celular y Viral, Unidad de Virolog\u00eda IUETSPC, Unidad de Farmacolog\u00eda, Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna (ULL), Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"M\u00e1rquez-Arce","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Celular y Viral, Unidad de Virolog\u00eda IUETSPC, Unidad de Farmacolog\u00eda, Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna (ULL), Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Pernas","sequence":"additional","affiliation":[{"name":"Unidad de Virologia Molecular, Laboratorio de Referencia e Investigaci\u00f3n en Retrovirus, Centro Nacional de Microbiolog\u00eda (CNM), Instituto de Salud Carlos IIII, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00edlvia","family":"Marfil","sequence":"additional","affiliation":[{"name":"Institut de Recerca de la Sida IrsiCaixa, Institut d\u2019Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol (IGTP), Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Borr\u00e0s-Gra\u00f1ana","sequence":"additional","affiliation":[{"name":"Institut de Recerca de la Sida IrsiCaixa, Institut d\u2019Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol (IGTP), Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Olivares","sequence":"additional","affiliation":[{"name":"Unidad de Virologia Molecular, Laboratorio de Referencia e Investigaci\u00f3n en Retrovirus, Centro Nacional de Microbiolog\u00eda (CNM), Instituto de Salud Carlos IIII, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Cabrera-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Celular y Viral, Unidad de Virolog\u00eda IUETSPC, Unidad de Farmacolog\u00eda, Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna (ULL), Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda-Soledad","family":"Valera","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Celular y Viral, Unidad de Virolog\u00eda IUETSPC, Unidad de Farmacolog\u00eda, Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna (ULL), Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"de Armas-Rillo","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Celular y Viral, Unidad de Virolog\u00eda IUETSPC, Unidad de Farmacolog\u00eda, Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna (ULL), Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Lemey","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Rega Institute, KU Leuven, University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli\u00e0","family":"Blanco","sequence":"additional","affiliation":[{"name":"Institut de Recerca de la Sida IrsiCaixa, Institut d\u2019Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol (IGTP), Badalona, Spain"},{"name":"Universitat de Vic, Universitat Central de Catalunya, UVIC, Vic, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00edn","family":"Valenzuela-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Celular y Viral, Unidad de Virolog\u00eda IUETSPC, Unidad de Farmacolog\u00eda, Secci\u00f3n de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna (ULL), Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2324-9584","authenticated-orcid":false,"given":"Cecilio","family":"Lopez-Gal\u00edndez","sequence":"additional","affiliation":[{"name":"Unidad de Virologia Molecular, Laboratorio de Referencia e Investigaci\u00f3n en Retrovirus, Centro Nacional de Microbiolog\u00eda (CNM), Instituto de Salud Carlos IIII, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199408000-00014"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011079"},{"key":"e_1_3_2_4_2","first-page":"261","article-title":"Control of HIV-1 replication in elite suppressors","volume":"9","author":"Blankson JN","year":"2010","unstructured":"Blankson JN. 2010. Control of HIV-1 replication in elite suppressors. Discov Med 9:261\u2013266.","journal-title":"Discov Med"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/433188"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000049"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050567397"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611244104"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.22.10581-10588.2000"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.9.4361-4376.2000"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030330"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000377"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00286-10"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2009.05.022"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5265.1167"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243727"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2001855"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001123"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1421607112"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000876"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004565"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/emph\/eot019"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004634"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199905280-00006"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6880"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.16.9069-9073.2003"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.11.7121-7134.2005"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)92628-7"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.12.5646-5655.2001"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.035873"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-10-39"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.266pe23"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103845"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E05-04-0354"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2008.04.003"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077663"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7824947"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-014-0081-0"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.19.10752"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.12.10489-10502.1999"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.11.039"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.10.6882"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408547200"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-6-89"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.12.10310-10319.1999"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00839-09"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-4-89"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E10-08-0722"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-015-0181-5"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.02338-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.02338-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T21:12:13Z","timestamp":1646687533000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.02338-17"}},"subtitle":[],"editor":[{"given":"Dimitrios","family":"Paraskevis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,5,2]]},"references-count":48,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,5,2]]}},"alternative-id":["10.1128\/mBio.02338-17"],"URL":"https:\/\/doi.org\/10.1128\/mbio.02338-17","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.733024960.793547576","asserted-by":"object"}]},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,2]]},"assertion":[{"value":"2017-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02338-17"}}