PLoS Pathogens (May 2010)

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

  • Hui Li,
  • Katharine J Bar,
  • Shuyi Wang,
  • Julie M Decker,
  • Yalu Chen,
  • Chuanxi Sun,
  • Jesus F Salazar-Gonzalez,
  • Maria G Salazar,
  • Gerald H Learn,
  • Charity J Morgan,
  • Joseph E Schumacher,
  • Peter Hraber,
  • Elena E Giorgi,
  • Tanmoy Bhattacharya,
  • Bette T Korber,
  • Alan S Perelson,
  • Joseph J Eron,
  • Myron S Cohen,
  • Charles B Hicks,
  • Barton F Haynes,
  • Martin Markowitz,
  • Brandon F Keele,
  • Beatrice H Hahn,
  • George M Shaw

DOI
https://doi.org/10.1371/journal.ppat.1000890
Journal volume & issue
Vol. 6, no. 5
p. e1000890

Abstract

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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.