{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T22:09:22Z","timestamp":1771884562166,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1008537","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100003896","name":"Henry M. Jackson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003896","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Department of the Army","award":["W81XWH-07-2-0067"],"award-info":[{"award-number":["W81XWH-07-2-0067"]}]},{"name":"U.S. Department of the Army","award":["W81XWH-11-2-0174"],"award-info":[{"award-number":["W81XWH-11-2-0174"]}]},{"name":"U.S. Department of the Army","award":["W81XWH-18-2-0040"],"award-info":[{"award-number":["W81XWH-18-2-0040"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>While large datasets of HIV-1 sequences are increasingly being generated, many studies rely on a single gene or fragment of the genome and few comparative studies across genes have been done. We performed genome-based and gene-specific Bayesian phylogenetic analyses to investigate how certain factors impact estimates of the infection dates in an acute HIV-1 infection cohort, RV217. In this cohort, HIV-1 diagnosis corresponded to the first RNA positive test and occurred a median of four days after the last negative test, allowing us to compare timing estimates using BEAST to a narrow window of infection. We analyzed HIV-1 sequences sampled one week, one month and six months after HIV-1 diagnosis in 39 individuals. We found that shared diversity and temporal signal was limited in acute infection, and insufficient to allow timing inferences in the shortest HIV-1 genes, thus dated phylogenies were primarily analyzed for<jats:italic>env<\/jats:italic>,<jats:italic>gag<\/jats:italic>,<jats:italic>pol<\/jats:italic>and near full-length genomes. There was no one best-fitting model across participants and genes, though relaxed molecular clocks (73% of best-fitting models) and the Bayesian skyline (49%) tended to be favored. For infections with single founders, the infection date was estimated to be around one week pre-diagnosis for<jats:italic>env<\/jats:italic>(IQR: 3\u20139 days) and<jats:italic>gag<\/jats:italic>(IQR: 5\u20139 days), whilst the genome placed it at a median of 10 days (IQR: 4\u201319). Multiply-founded infections proved problematic to date. Our ability to compare timing inferences to precise estimates of HIV-1 infection (within a week) highlights that molecular dating methods can be applied to within-host datasets from early infection. Nonetheless, our results also suggest caution when using uniform clock and population models or short genes with limited information content.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1008537","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T22:40:20Z","timestamp":1612219220000},"page":"e1008537","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Factors influencing estimates of HIV-1 infection timing using 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Inference of Lineage-Specific Birth and Death Rates","author":"J Barido-Sottani","year":"2020","journal-title":"Systematic Biology"},{"key":"pcbi.1008537.ref044","doi-asserted-by":"crossref","first-page":"20150420","DOI":"10.1098\/rspb.2015.0420","article-title":"How well can the exponential-growth coalescent approximate constant-rate birth\u2013death population dynamics?","volume":"282","author":"T Stadler","year":"2015","journal-title":"Proceedings of the Royal Society B"},{"key":"pcbi.1008537.ref045","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/bioinformatics\/16.4.400","article-title":"Detecting hypermutations in viral sequences with an emphasis on G\u2192A hypermutation","volume":"16","author":"PP Rose","year":"2000","journal-title":"Bioinformatics"},{"key":"pcbi.1008537.ref046","author":"WP Maddison","year":"2017","journal-title":"Mesquite: a modular system for evolutionary 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