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Recombination elevates the effective evolutionary rate and facilitates the establishment of HIV-1 infection in infants after mother-to-child transmission

BACKGROUND: Previous studies have demonstrated that single HIV-1 genotypes are commonly transmitted from mother to child, but such analyses primarily used single samples from mother and child. It is possible that in a single sample, obtained early after infection, only the most replication competent...

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Autores principales: Sanborn, Keri B., Somasundaran, Mohan, Luzuriaga, Katherine, Leitner, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647327/
https://www.ncbi.nlm.nih.gov/pubmed/26573574
http://dx.doi.org/10.1186/s12977-015-0222-0
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author Sanborn, Keri B.
Somasundaran, Mohan
Luzuriaga, Katherine
Leitner, Thomas
author_facet Sanborn, Keri B.
Somasundaran, Mohan
Luzuriaga, Katherine
Leitner, Thomas
author_sort Sanborn, Keri B.
collection PubMed
description BACKGROUND: Previous studies have demonstrated that single HIV-1 genotypes are commonly transmitted from mother to child, but such analyses primarily used single samples from mother and child. It is possible that in a single sample, obtained early after infection, only the most replication competent virus is detected even when other forms may have been transmitted. Such forms may have advantages later in infection, and may thus be detected in follow-up samples. Because HIV-1 frequently recombines, phylogenetic analyses that ignore recombination may miss transmission of multiple forms if they recombine after transmission. Moreover, recombination may facilitate adaptation, thus providing an advantage in establishing infection. The effect of recombination on viral evolution in HIV-1 infected children has not been well defined. RESULTS: We analyzed full-length env sequences after single genome amplification from the plasma of four subtype B HIV-1 infected women (11–67 env clones from 1 time point within a month prior to delivery) and their non-breastfed, intrapartum-infected children (3–6 longitudinal time points per child starting at the time of HIV-1 diagnosis). To address the potential beneficial or detrimental effects of recombination, we used a recently developed hierarchical recombination detection method based on the pairwise homoplasy index (PHI)-test. Recombination was observed in 9–67 % of the maternal sequences and in 25–60 % of the child sequences. In the child, recombination only occurred between variants that had evolved after transmission; taking recombination into account, we identified transmission of only 1 or 2 phylogenetic lineages from mother to child. Effective HIV-1 evolutionary rates of HIV-1 were initially high in the child and slowed over time (after 1000 days). Recombination was associated with elevated evolutionary rates. CONCLUSIONS: Our results confirm that 1–2 variants are typically transmitted from mothers to their newborns. They also demonstrate that early abundant recombination elevates the effective evolutionary rate, suggesting that recombination increases the rate of adaptation in HIV-1 evolution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-015-0222-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-46473272015-11-18 Recombination elevates the effective evolutionary rate and facilitates the establishment of HIV-1 infection in infants after mother-to-child transmission Sanborn, Keri B. Somasundaran, Mohan Luzuriaga, Katherine Leitner, Thomas Retrovirology Research BACKGROUND: Previous studies have demonstrated that single HIV-1 genotypes are commonly transmitted from mother to child, but such analyses primarily used single samples from mother and child. It is possible that in a single sample, obtained early after infection, only the most replication competent virus is detected even when other forms may have been transmitted. Such forms may have advantages later in infection, and may thus be detected in follow-up samples. Because HIV-1 frequently recombines, phylogenetic analyses that ignore recombination may miss transmission of multiple forms if they recombine after transmission. Moreover, recombination may facilitate adaptation, thus providing an advantage in establishing infection. The effect of recombination on viral evolution in HIV-1 infected children has not been well defined. RESULTS: We analyzed full-length env sequences after single genome amplification from the plasma of four subtype B HIV-1 infected women (11–67 env clones from 1 time point within a month prior to delivery) and their non-breastfed, intrapartum-infected children (3–6 longitudinal time points per child starting at the time of HIV-1 diagnosis). To address the potential beneficial or detrimental effects of recombination, we used a recently developed hierarchical recombination detection method based on the pairwise homoplasy index (PHI)-test. Recombination was observed in 9–67 % of the maternal sequences and in 25–60 % of the child sequences. In the child, recombination only occurred between variants that had evolved after transmission; taking recombination into account, we identified transmission of only 1 or 2 phylogenetic lineages from mother to child. Effective HIV-1 evolutionary rates of HIV-1 were initially high in the child and slowed over time (after 1000 days). Recombination was associated with elevated evolutionary rates. CONCLUSIONS: Our results confirm that 1–2 variants are typically transmitted from mothers to their newborns. They also demonstrate that early abundant recombination elevates the effective evolutionary rate, suggesting that recombination increases the rate of adaptation in HIV-1 evolution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-015-0222-0) contains supplementary material, which is available to authorized users. BioMed Central 2015-11-16 /pmc/articles/PMC4647327/ /pubmed/26573574 http://dx.doi.org/10.1186/s12977-015-0222-0 Text en © Sanborn et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sanborn, Keri B.
Somasundaran, Mohan
Luzuriaga, Katherine
Leitner, Thomas
Recombination elevates the effective evolutionary rate and facilitates the establishment of HIV-1 infection in infants after mother-to-child transmission
title Recombination elevates the effective evolutionary rate and facilitates the establishment of HIV-1 infection in infants after mother-to-child transmission
title_full Recombination elevates the effective evolutionary rate and facilitates the establishment of HIV-1 infection in infants after mother-to-child transmission
title_fullStr Recombination elevates the effective evolutionary rate and facilitates the establishment of HIV-1 infection in infants after mother-to-child transmission
title_full_unstemmed Recombination elevates the effective evolutionary rate and facilitates the establishment of HIV-1 infection in infants after mother-to-child transmission
title_short Recombination elevates the effective evolutionary rate and facilitates the establishment of HIV-1 infection in infants after mother-to-child transmission
title_sort recombination elevates the effective evolutionary rate and facilitates the establishment of hiv-1 infection in infants after mother-to-child transmission
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647327/
https://www.ncbi.nlm.nih.gov/pubmed/26573574
http://dx.doi.org/10.1186/s12977-015-0222-0
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