title: High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men.
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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Katharine J
authors.initials: KJ
authors.lastname: Bar
authors.forename: Shuyi
authors.initials: S
authors.lastname: Wang
authors.forename: Julie M
authors.initials: JM
authors.lastname: Decker
authors.forename: Yalu
authors.initials: Y
authors.lastname: Chen
authors.forename: Chuanxi
authors.initials: C
authors.lastname: Sun
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Salazar-Gonzalez
authors.forename: Maria G
authors.initials: MG
authors.lastname: Salazar
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Learn
authors.forename: Charity J
authors.initials: CJ
authors.lastname: Morgan
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Schumacher
authors.forename: Peter
authors.initials: P
authors.lastname: Hraber
authors.forename: Elena E
authors.initials: EE
authors.lastname: Giorgi
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Bhattacharya
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: Myron S
authors.initials: MS
authors.lastname: Cohen
authors.forename: Charles B
authors.initials: CB
authors.lastname: Hicks
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Martin
authors.initials: M
authors.lastname: Markowitz
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
mesh_terms: D004196:Disease Outbreaks / Q000706:statistics & numerical data; D019143:Evolution, Molecular; D014644:Genetic Variation; D016679:Genome, Viral; D015658:HIV Infections / Q000453:epidemiology / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development* / Q000472:pathogenicity; D020010:Heterosexuality / Q000706:statistics & numerical data; D018451:Homosexuality, Male / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008957:Models, Genetic; D011995:Recombination, Genetic / Q000235:genetics; D012307:Risk Factors; D012725:Sexual Behavior / Q000706:statistics & numerical data*; D014774:Virulence; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D054299:env Gene Products, Human Immunodeficiency Virus