Show simple item record

dc.creatorTully, DC
dc.creatorOgilvie, CB
dc.creatorBatorsky, RE
dc.creatorBean, DJ
dc.creatorPower, KA
dc.creatorGhebremichael, M
dc.creatorBedard, HE
dc.creatorGladden, AD
dc.creatorSeese, AM
dc.creatorAmero, MA
dc.creatorLane, K
dc.creatorMcGrath, G
dc.creatorBazner, SB
dc.creatorTinsley, J
dc.creatorLennon, NJ
dc.creatorHenn, MR
dc.creatorBrumme, ZL
dc.creatorNorris, PJ
dc.creatorRosenberg, ES
dc.creatorMayer, KH
dc.creatorJessen, H
dc.creatorKosakovsky Pond, SL
dc.creatorWalker, BD
dc.creatorAltfeld, M
dc.creatorCarlson, JM
dc.creatorAllen, TM
dc.identifier.other27163788 (pubmed)
dc.description.abstract© 2016 Tully et al. Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic “signatures” within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission.
dc.relation.haspartPLoS Pathogens
dc.relation.isreferencedbyPublic Library of Science (PLoS)
dc.rightsCC BY
dc.subjectEvolution, Molecular
dc.subjectGenetic Variation
dc.subjectGenome, Viral
dc.subjectHIV Envelope Protein gp120
dc.subjectHIV Infections
dc.subjectModels, Theoretical
dc.subjectPolymerase Chain Reaction
dc.subjectSelection, Genetic
dc.titleDifferences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus
dc.type.genreJournal Article
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact
dc.creator.orcidPond, Sergei L. Kosakovsky|0000-0003-4817-4029

Files in this item

Differences in the Selection ...

This item appears in the following Collection(s)

Show simple item record

Except where otherwise noted, this item's license is described as CC BY