Show simple item record Li, H Bar, KJ Wang, S Decker, JM Chen, Y Sun, C Salazar-Gonzalez, JF Salazar, MG Learn, GH Morgan, CJ al, E 2011-06-21T17:32:22Z 2010
dc.identifier.citation PLoS pathogens, 2010, 6 (5), pp. e1000890 - ?
dc.identifier.issn 1553-7374
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.format.extent e1000890 - ?
dc.language.iso en_US 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 en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-5-0 en_US
duke.description.endpage e1000890 en_US
duke.description.issue 5 en_US
duke.description.startpage e1000890 en_US
duke.description.volume 6 en_US
dc.relation.journal Plos Pathogens en_US
pubs.issue 5
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Faculty
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Immunology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Duke Human Vaccine Institute
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Human Vaccine Institute
pubs.organisational-group /Duke/University Institutes and Centers
pubs.organisational-group /Duke/University Institutes and Centers/Global Health Institute
pubs.volume 6

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