{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:24:41Z","timestamp":1787016281961,"version":"build-2736575974"},"reference-count":86,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"36","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,9,5]]},"abstract":"<jats:p>\n                    HIV-1 evades immune responses by modulating plasma membrane receptors. Using a flow cytometry\u2013based screening, we profiled 332 surface receptors on HIV-1\u2013infected primary CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and identified 23 down-regulated receptors, including known targets such as CD4, MHCI, CCR7, and CD62L. CD96, an inhibitory natural killer (NK) cell receptor poorly studied in human CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, was markedly down-regulated. This modulation, mediated by the viral proteins Nef and Vpu, surpassed that of other NK-associated receptors such as CD155 and NTB-A and is conserved across lentiviruses. CD96\n                    <jats:sup>Hi<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells exhibited a proinflammatory T\n                    <jats:sub>H<\/jats:sub>\n                    1\/T\n                    <jats:sub>H<\/jats:sub>\n                    17 phenotype characterized by IFN-\u03b3 and IL-17 secretion and displayed impaired migration in vivo. Furthermore, CD96 ligation enhanced IFN-\u03b3 release upon viral peptide stimulation and promoted the secretion of T\n                    <jats:sub>H<\/jats:sub>\n                    1\/T\n                    <jats:sub>H<\/jats:sub>\n                    17-associated cytokines. Our findings suggest that CD96 regulates antiviral immune responses and maintains proinflammatory properties in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Thus, its down-regulation represents a previously unknown HIV-1 immune evasion strategy, with implications for exploiting CD96 as immunotherapeutic target.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adx7485","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T17:58:29Z","timestamp":1757095109000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["HIV-1 manipulates CD96 on CD4\n                    <sup>+<\/sup>\n                    T cells to subvert antiviral immunity"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5727-5396","authenticated-orcid":true,"given":"Sandra","family":"Dehn","sequence":"first","affiliation":[{"name":"Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital T\u00fcbingen, T\u00fcbingen, 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Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Brandimarte","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2158-4981","authenticated-orcid":true,"given":"Dinah","family":"Heiligensetzer","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herwig","family":"Koppensteiner","sequence":"additional","affiliation":[{"name":"Institute of Virology, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Neuherberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7368-7523","authenticated-orcid":true,"given":"Baubak","family":"Bajoghli","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology, Immunology and Rheumatology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Hailfinger","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital M\u00fcnster, M\u00fcnster, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Schilbach","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Children\u2019s Hospital T\u00fcbingen, T\u00fcbingen, 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