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High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men.

dc.contributor.author al, E
dc.contributor.author Bar, KJ
dc.contributor.author Chen, Y
dc.contributor.author Decker, JM
dc.contributor.author Learn, Gerald H
dc.contributor.author Li, H
dc.contributor.author Morgan, CJ
dc.contributor.author Salazar-Gonzalez, JF
dc.contributor.author Salazar, MG
dc.contributor.author Sun, C
dc.contributor.author Wang, S
dc.date.accessioned 2011-06-21T17:32:22Z
dc.date.issued 2010
dc.identifier.issn 1553-7374
dc.identifier.uri https://hdl.handle.net/10161/4599
dc.description.abstract Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5' and 3' half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3-6 days before symptom onset and 14-17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized.
dc.language.iso en_US
dc.relation.ispartof PLoS pathogens
dc.relation.isversionof 10.1371/journal.ppat.1000890
dc.title High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men.
dc.title.alternative
dc.type Journal article
dc.description.version Version of Record
duke.date.pubdate 2010-5-0
duke.description.issue 5
duke.description.volume 6
dc.relation.journal Plos Pathogens
pubs.begin-page e1000890
pubs.issue 5
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Human Vaccine Institute
pubs.organisational-group Faculty
pubs.organisational-group Global Health Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Duke Human Vaccine Institute
pubs.organisational-group School of Medicine
pubs.organisational-group University Institutes and Centers
pubs.volume 6


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