{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:32:37Z","timestamp":1791282757127,"version":"4.1.0"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2014,3,15]],"date-time":"2014-03-15T00:00:00Z","timestamp":1394841600000},"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":[[2014,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Elite controllers or suppressors (ES) are HIV-1-infected patients who maintain undetectable viral loads without antiretroviral therapy. The mechanism of control remains unclear, but the HLA-B*57 allele is overrepresented in cohorts of these patients. However, many HLA-B*57 patients develop progressive disease, and some studies have suggested that infection with defective viruses may be the cause of the lack of high levels of virus replication and disease progression in ES. We therefore performed a comprehensive comparative\n            <jats:italic>in vivo<\/jats:italic>\n            and\n            <jats:italic>in vitro<\/jats:italic>\n            characterization of viruses isolated from well-defined ES. For this purpose, we first performed full-genome sequence analysis and\n            <jats:italic>in vitro<\/jats:italic>\n            fitness assays on replication-competent isolates from HLA-B*57 ES and HLA-B*57 chronic progressors (CPs). Under our experimental conditions, we found that isolates from ES and CPs can replicate\n            <jats:italic>in vitro<\/jats:italic>\n            . However, since inherently these assays involve the use of unnaturally\n            <jats:italic>in vitro<\/jats:italic>\n            -activated cells, we also investigated the replication competence and pathogenic potential of these HIV isolates\n            <jats:italic>in vivo<\/jats:italic>\n            using humanized BLT mice. The results from these analyses demonstrate that virus isolates from ES are fully replication competent\n            <jats:italic>in vivo<\/jats:italic>\n            and can induce peripheral and systemic CD4 T cell depletion. These results provide the first direct\n            <jats:italic>in vivo<\/jats:italic>\n            evidence that viral fitness does not likely determine clinical outcome in HLA-B*57 patients and that elite suppressors can control replication-competent, fully pathogenic viruses. A better understanding of the immunological bases of viral suppression in ES will serve to inform novel approaches to preventive and therapeutic HIV vaccine design.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Elite suppressors are HIV-1-infected patients who have undetectable levels of viremia despite not being on antiviral drugs. One of the most fundamental questions about this phenomenon involves the mechanism of control. To address this question, we isolated virus from elite suppressors and from HIV-1-infected patients who have the usual progressive disease course. We compared how well the isolates from the two groups of patients replicated in culture and in humanized mice. Our results suggest that elite suppressors are capable of controlling HIV-1 due to the possession of unique host factors rather than infection with defective virus.\n          <\/jats:p>","DOI":"10.1128\/jvi.03380-13","type":"journal-article","created":{"date-parts":[[2014,1,4]],"date-time":"2014-01-04T03:26:15Z","timestamp":1388805975000},"page":"3340-3352","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["HLA-B*57 Elite Suppressor and Chronic Progressor HIV-1 Isolates Replicate Vigorously and Cause CD4\n            <sup>+<\/sup>\n            T Cell Depletion in Humanized BLT Mice"],"prefix":"10.1128","volume":"88","author":[{"given":"Maria","family":"Salgado","sequence":"first","affiliation":[{"name":"Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"AIDS Research Institute IrsiCaixa, Institut d'Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Swanson","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Pohlmeyer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Robert W.","family":"Buckheit","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancie M.","family":"Archin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Margolis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Siliciano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Victor","family":"Garcia","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel N.","family":"Blankson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for AIDS Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.08.010"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.925"},{"key":"e_1_3_3_4_2","first-page":"261","article-title":"Control of HIV-1 replication in elite suppressors","volume":"9","author":"Blankson JN","year":"2010","unstructured":"BlanksonJN. 2010. 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