{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T09:15:39Z","timestamp":1780823739888,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012434","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000}}],"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001852","name":"CEFIPRA","doi-asserted-by":"crossref","award":["64T4-2"],"award-info":[{"award-number":["64T4-2"]}],"id":[{"id":"10.13039\/501100001852","id-type":"DOI","asserted-by":"crossref"}]},{"name":"French National Agency of AIDS and Viral Hepatitis Research"},{"DOI":"10.13039\/100016913","name":"MSDAVENIR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016913","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programme Investissements d\u2019Avenir","award":["ANR\u201011\u2010INBS\u20100008, ANR\u201010\u2010EQPX\u201002\u201001"],"award-info":[{"award-number":["ANR\u201011\u2010INBS\u20100008, ANR\u201010\u2010EQPX\u201002\u201001"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>While most individuals suffer progressive disease following HIV infection, a small fraction spontaneously controls the infection. Although CD8 T-cells have been implicated in this natural control, their mechanistic roles are yet to be established. Here, we combined mathematical modeling and analysis of previously published data from 16 SIV-infected macaques, of which 12 were natural controllers, to elucidate the role of CD8 T-cells in natural control. For each macaque, we considered, in addition to the canonical <jats:italic>in vivo<\/jats:italic> plasma viral load and SIV DNA data, longitudinal <jats:italic>ex vivo<\/jats:italic> measurements of the virus suppressive capacity of CD8 T-cells. Available mathematical models do not allow analysis of such combined <jats:italic>in vivo<\/jats:italic>-<jats:italic>ex vivo<\/jats:italic> datasets. We explicitly modeled the <jats:italic>ex vivo<\/jats:italic> assay, derived analytical approximations that link the <jats:italic>ex vivo<\/jats:italic> measurements with the <jats:italic>in vivo<\/jats:italic> effector function of CD8-T cells, and integrated them with an <jats:italic>in vivo<\/jats:italic> model of virus dynamics, thus developing a new learning framework that enabled the analysis. Our model fit the data well and estimated the recruitment rate and\/or maximal killing rate of CD8 T-cells to be up to 2-fold higher in controllers than non-controllers (p = 0.013). Importantly, the cumulative suppressive capacity of CD8 T-cells over the first 4\u20136 weeks of infection was associated with virus control (Spearman\u2019s \u03c1 = -0.51; p = 0.05). Thus, our analysis identified the early cumulative suppressive capacity of CD8 T-cells as a predictor of natural control. Furthermore, simulating a large virtual population, our model quantified the minimum capacity of this early CD8 T-cell response necessary for long-term control. Our study presents new, quantitative insights into the role of CD8 T-cells in the natural control of HIV infection and has implications for remission strategies.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012434","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T17:34:28Z","timestamp":1725989668000},"page":"e1012434","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Antiviral capacity of the early CD8 T-cell response is predictive of natural control of SIV infection: Learning in vivo dynamics using ex vivo data"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9469-1847","authenticated-orcid":true,"given":"Bharadwaj","family":"Vemparala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Madelain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Passaes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Millet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7022-2990","authenticated-orcid":true,"given":"V\u00e9ronique","family":"Avettand-Fenoel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rams\u00e8s","family":"Djidjou-Demasse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Dereuddre-Bosquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Le Grand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Rouzioux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Vaslin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asier","family":"S\u00e1ez-Ciri\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9mie","family":"Guedj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2145-9828","authenticated-orcid":true,"given":"Narendra 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