Abstract
BackgroundPrevious 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.ResultsWe 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.ConclusionsOur 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 materialThe online version of this article (doi:10.1186/s12977-015-0222-0) contains supplementary material, which is available to authorized users.
Highlights
Previous studies have demonstrated that single human immunodeficiency virus (HIV)-1 genotypes are commonly transmitted from mother to child, but such analyses primarily used single samples from mother and child
We evaluated HIV-1 env sequences obtained from samples collected longitudinally from four mother–child pairs (1) to evaluate what effects recombination may have on HIV-1 transmission and the subsequent evolutionary rate, and (2) to determine the number of variants transmitted from mother to child
Note that when the ancestral sequences of the recombinant are genetically similar, there should be less of a biological impact of recombination, and the detection ability should to some degree follow the general genetic diversity in the recombining population
Summary
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. Because HIV-1 frequently recombines, phylogenetic analyses that ignore recombination may miss transmission of multiple forms if they recombine after transmission. While the role of recombination in the establishment of HIV-1 infection is unknown, evolutionary theory suggests [11,12,13,14,15,16] that recombination may alter the genetic variation upon which natural selection can operate. This would likely increase the overall evolutionary rate. Because recombination may be fundamentally important to HIV-1 infection and evolution, and because recombination may interfere with standard phylogenetic analyses, it is important to consider potential recombinants in the assessment of HIV-1 transmission
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