High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men.
| dc.contributor.author | Li, H | |
| dc.contributor.author | Bar, KJ | |
| dc.contributor.author | Wang, S | |
| dc.contributor.author | Decker, JM | |
| dc.contributor.author | Chen, Y | |
| dc.contributor.author | Sun, C | |
| dc.contributor.author | Salazar Gonzalez, JF | |
| dc.contributor.author | Salazar, MG | |
| dc.contributor.author | Learn, GH | |
| dc.contributor.author | Morgan, CJ | |
| dc.contributor.author | Schumacher, JE | |
| dc.contributor.author | Hraber, P | |
| dc.contributor.author | Giorgi, EE | |
| dc.contributor.author | Bhattacharya, T | |
| dc.contributor.author | Korber, BT | |
| dc.contributor.author | Perelson, AS | |
| dc.contributor.author | Eron, JJ | |
| dc.contributor.author | Cohen, MS | |
| dc.contributor.author | Hicks, CB | |
| dc.contributor.author | Haynes, BF | |
| dc.contributor.author | Markowitz, M | |
| dc.contributor.author | Keele, BF | |
| dc.contributor.author | Hahn, BH | |
| dc.contributor.author | Shaw, GM | |
| dc.contributor.editor | Douek, Daniel C | |
| dc.date.accessioned | 2011-06-21T17:32:22Z | |
| dc.date.issued | 2010 | |
| 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.description.version | Version of Record | |
| dc.identifier.issn | 1553-7374 | |
| dc.identifier.uri | ||
| dc.language.iso | en_US | |
| dc.publisher | Public Library of Science (PLoS) | |
| dc.relation.ispartof | PLoS pathogens | |
| dc.relation.isversionof | 10.1371/journal.ppat.1000890 | |
| dc.relation.journal | Plos Pathogens | |
| dc.title | High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men. | |
| dc.title.alternative | ||
| dc.type | Journal article | |
| duke.date.pubdate | 2010-5-0 | |
| duke.description.issue | 5 | |
| duke.description.volume | 6 | |
| 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 |