Estimates of HIV-1 within-host recombination rates across the whole genome

Recombination plays a pivotal role in generating within-host diversity and enabling HIV's evolutionary success, particularly in evading the host immune response. Despite this, the variability in recombination rates across different settings and the underlying factors that drive these differences remain poorly understood. In this study, we analysed a large dataset encompassing hundreds of untreated, longitudinally sampled infections using both whole-genome long-read and short-read sequencing datasets. By quantifying recombination rates, we uncover substantial variation across subtypes, viral loads, and stages of infection. We also map recombination hot and cold spots across the genome using a sliding window approach, finding that previously reported inter-subtype regions of high or low recombination are replicated at the within-host level. Importantly, our findings reveal the significant influence of selection on recombination, showing that the presence and success of recombinant genomes is strongly interconnected with the fitness landscape. These results offer valuable insights into the contribution of recombination to evolutionary dynamics and demonstrate the enhanced resolution that long-read sequencing offers for studying viral evolution.

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Publication Details

Journal
Virus Evolution
Published
2025-01-01
DOI
https://doi.org/10.1093/ve/veaf052
Citations
1
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
1.04
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article

Estimates of HIV-1 within-host recombination rates across the whole genome

Emma C. Thomson, Jairam R. Lingappa, David Bonsall, George MacIntyre-Cockett et al.
1 citations
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article

Estimates of HIV-1 within-host recombination rates across the whole genome

Emma C. Thomson, Jairam R. Lingappa, David Bonsall, George MacIntyre-Cockett, Nicholas Grayson, Sandra E Chaudron, Joshua T. Herbeck, Andrew Mujugira, Katrina Lythgoe, Christophe Fraser, Harriet Longley
article en
1 citations

Abstract

Recombination plays a pivotal role in generating within-host diversity and enabling HIV's evolutionary success, particularly in evading the host immune response. Despite this, the variability in recombination rates across different settings and the underlying factors that drive these differences remain poorly understood. In this study, we analysed a large dataset encompassing hundreds of untreated, longitudinally sampled infections using both whole-genome long-read and short-read sequencing datasets. By quantifying recombination rates, we uncover substantial variation across subtypes, viral loads, and stages of infection. We also map recombination hot and cold spots across the genome using a sliding window approach, finding that previously reported inter-subtype regions of high or low recombination are replicated at the within-host level. Importantly, our findings reveal the significant influence of selection on recombination, showing that the presence and success of recombinant genomes is strongly interconnected with the fitness landscape. These results offer valuable insights into the contribution of recombination to evolutionary dynamics and demonstrate the enhanced resolution that long-read sequencing offers for studying viral evolution.

Virus EvolutionVol. 11(1)
Gates Foundation (US), Centre for Human Genetics (GB), University of Washington (US), Angkor Hospital for Children (KH), Nuffield Orthopaedic Centre (GB), University of Oxford (GB), Seattle University (US), Makerere University (UG)
Good health and well-being
Openalex Percentile: Top 22%
HIV Research and Treatment
1.04
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