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

  1. Author:
    Li, H.
    Bar, K. J.
    Wang, S. Y.
    Decker, J. M.
    Chen, Y. L.
    Sun, C. X.
    Salazar-Gonzalez, J. F.
    Salazar, M. G.
    Learn, G. H.
    Morgan, C. J.
    Schumacher, J. E.
    Hraber, P.
    Giorgi, E. E.
    Bhattacharya, T.
    Korber, B. T.
    Perelson, A. S.
    Eron, J. J.
    Cohen, M. S.
    Hicks, C. B.
    Haynes, B. F.
    Markowitz, M.
    Keele, B. F.
    Hahn, B. H.
    Shaw, G. M.

  2. Author Address

    [Li, Hui; Bar, Katharine J.; Wang, Shuyi; Decker, Julie M.; Chen, Yalu; Sun, Chuanxi; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Learn, Gerald H.; Schumacher, Joseph E.; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Morgan, Charity J.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Hraber, Peter; Giorgi, Elena E.; Bhattacharya, Tanmoy; Korber, Bette T.; Perelson, Alan S.] Los Alamos Natl Lab, Los Alamos, NM USA. [Giorgi, Elena E.] Univ Massachusetts, Dept Math & Stat, Amherst, MA 01003 USA. [Bhattacharya, Tanmoy; Korber, Bette T.] Santa Fe Inst, Santa Fe, NM 87501 USA. [Eron, Joseph J.; Cohen, Myron S.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Hicks, Charles B.; Haynes, Barton F.] Duke Univ, Dept Med, Durham, NC USA. [Markowitz, Martin] Aaron Diamond AIDS Res Ctr, New York, NY USA. [Markowitz, Martin] Rockefeller Univ, New York, NY 10021 USA. [Keele, Brandon F.] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.;Li, H, Univ Alabama, Dept Med, Birmingham, AL 35294 USA.;gshaw@uab.edu
    1. Year: 2010
    2. Date: May
  2. Journal: Plos Pathogens
    1. 6
    2. 5
    3. Pages: 17
  4. Type of Article: Article
  5. Article Number: e1000890
  6. ISSN: 1553-7366
  1. 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.

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External Sources

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  2. DOI: 10.1371/journal.ppat.1000890
  3. View record in Web of Science®
  4. WOS: 000278759900012

Library Notes

  1. Fiscal Year: FY2009-2010
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