UMMS Affiliation

Program in Molecular Medicine; Department of Pediatrics, Division of Immunology/Infectious Disease

Publication Date

11-16-2015

Document Type

Article

Disciplines

Genetics | Immunology of Infectious Disease | Maternal and Child Health | Pediatrics | Virology

Abstract

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.

Rights and Permissions

Citation: Retrovirology. 2015 Nov 16;12:96. doi: 10.1186/s12977-015-0222-0. Link to article on publisher's site

DOI of Published Version

10.1186/s12977-015-0222-0

Comments

This 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.

Related Resources

Link to Article in PubMed

Keywords

HIV-1, MTCT, Transmitted/founder virus, Recombination, Adaptation, Evolutionary rate

Journal/Book/Conference Title

Retrovirology

PubMed ID

26573574

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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