Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination

dc.contributor.authorBaird, Heather A
dc.contributor.authorGao, Yong
dc.contributor.authorGaletto, Román
dc.contributor.authorLalonde, Matthew
dc.contributor.authorAnthony, Reshma M
dc.contributor.authorGiacomoni, Véronique
dc.contributor.authorAbreha, Measho
dc.contributor.authorDestefano, Jeffrey J
dc.contributor.authorNegroni, Matteo
dc.contributor.authorArts, Eric J
dc.date.accessioned2021-12-07T20:44:02Z
dc.date.available2021-12-07T20:44:02Z
dc.date.issued2006-12-12
dc.description.abstractHIV-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.urihttps://doi.org/10.1186/1742-4690-3-91
dc.identifierhttps://doi.org/10.13016/ugqc-yjan
dc.identifier.citationBaird, 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.urihttp://hdl.handle.net/1903/28216
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.isAvailableAtCell Biology & Molecular Geneticsen_us
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtCollege of Computer, Mathematical & Natural Sciencesen_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.subjectRecombination Frequencyen_US
dc.subjectDual Infectionen_US
dc.subjectStrand Transferen_US
dc.subjectReplicative Fitnessen_US
dc.subjectHigh Recombination Frequencyen_US
dc.titleInfluence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombinationen_US
dc.typeArticleen_US

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