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Factors influencing estimates of HIV-1 infection timing using BEAST.
- Source :
-
PLoS Computational Biology . 2/1/2021, Vol. 17 Issue 2, p1-23. 23p. 7 Graphs. - Publication Year :
- 2021
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Abstract
- 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 env, gag, pol 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 env (IQR: 3–9 days) and gag (IQR: 5–9 days), whilst the genome placed it at a median of 10 days (IQR: 4–19). 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. Author summary: Molecular dating using phylogenetics allows us to estimate the date of an infection from time-stamped within-host sequences alone. There are large datasets of HIV-1 sequences, but genome and gene analyses are not often performed in parallel and rarely with the possibility to compare results against a known narrow window of infection. We showed that all but the longest genes are near-clonal in acute infection, with little information for dating purposes. For infections with single founders, we estimated the eclipse phase—the time between HIV-1 exposure and the first positive diagnostic test—to last between one and two weeks using env, gag, pol and near full-length genomes. This approach could be used to narrow the date of suspected infection in ongoing clinical trials for the prevention of HIV-1 infection. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HIV
*MOLECULAR clock
*GENES
*BAYESIAN analysis
*TIME management
*INFECTION
Subjects
Details
- Language :
- English
- ISSN :
- 1553734X
- Volume :
- 17
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- PLoS Computational Biology
- Publication Type :
- Academic Journal
- Accession number :
- 148435467
- Full Text :
- https://doi.org/10.1371/journal.pcbi.1008537