Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination
dc.contributor.author | Baird, Heather A | |
dc.contributor.author | Gao, Yong | |
dc.contributor.author | Galetto, Román | |
dc.contributor.author | Lalonde, Matthew | |
dc.contributor.author | Anthony, Reshma M | |
dc.contributor.author | Giacomoni, Véronique | |
dc.contributor.author | Abreha, Measho | |
dc.contributor.author | Destefano, Jeffrey J | |
dc.contributor.author | Negroni, Matteo | |
dc.contributor.author | Arts, Eric J | |
dc.date.accessioned | 2021-12-07T20:44:02Z | |
dc.date.available | 2021-12-07T20:44:02Z | |
dc.date.issued | 2006-12-12 | |
dc.description.abstract | HIV-1 recombination between different subtypes has a major impact on the global epidemic. The generation of these intersubtype recombinants follows a defined set of events starting with dual infection of a host cell, heterodiploid virus production, strand transfers during reverse transcription, and then selection. In this study, recombination frequencies were measured in the C1-C4 regions of the envelope gene in the presence (using a multiple cycle infection system) and absence (in vitro reverse transcription and single cycle infection systems) of selection for replication-competent virus. Ugandan subtypes A and D HIV-1 env sequences (115-A, 120-A, 89-D, 122-D, 126-D) were employed in all three assay systems. These subtypes co-circulate in East Africa and frequently recombine in this human population. Increased sequence identity between viruses or RNA templates resulted in increased recombination frequencies, with the exception of the 115-A virus or RNA template. Analyses of the recombination breakpoints and mechanistic studies revealed that the presence of a recombination hotspot in the C3/V4 env region, unique to 115-A as donor RNA, could account for the higher recombination frequencies with the 115-A virus/template. Single-cycle infections supported proportionally less recombination than the in vitro reverse transcription assay but both systems still had significantly higher recombination frequencies than observed in the multiple-cycle virus replication system. In the multiple cycle assay, increased replicative fitness of one HIV-1 over the other in a dual infection dramatically decreased recombination frequencies. Sequence variation at specific sites between HIV-1 isolates can introduce unique recombination hotspots, which increase recombination frequencies and skew the general observation that decreased HIV-1 sequence identity reduces recombination rates. These findings also suggest that the majority of intra- or intersubtype A/D HIV-1 recombinants, generated with each round of infection, are not replication-competent and do not survive in the multiple-cycle system. Ability of one HIV-1 isolate to outgrow the other leads to reduced co-infections, heterozygous virus production, and recombination frequencies. | en_US |
dc.description.uri | https://doi.org/10.1186/1742-4690-3-91 | |
dc.identifier | https://doi.org/10.13016/ugqc-yjan | |
dc.identifier.citation | Baird, H.A., Gao, Y., Galetto, R. et al. Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination. Retrovirology 3, 91 (2006). | en_US |
dc.identifier.uri | http://hdl.handle.net/1903/28216 | |
dc.language.iso | en_US | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation.isAvailableAt | Cell Biology & Molecular Genetics | en_us |
dc.relation.isAvailableAt | Digital Repository at the University of Maryland | en_us |
dc.relation.isAvailableAt | College of Computer, Mathematical & Natural Sciences | en_us |
dc.relation.isAvailableAt | University of Maryland (College Park, MD) | en_us |
dc.subject | Recombination Frequency | en_US |
dc.subject | Dual Infection | en_US |
dc.subject | Strand Transfer | en_US |
dc.subject | Replicative Fitness | en_US |
dc.subject | High Recombination Frequency | en_US |
dc.title | Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination | en_US |
dc.type | Article | en_US |
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