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

PLoS Pathogens

George M. Shaw¹  Charity J. Morgan²  Tanmoy Bhattacharya³  Beatrice H. Hahn⁴  Brandon F. Keele⁴  Jesus F. Salazar-Gonzalez⁵  Shuyi Wang⁵  Julie M. Decker⁵  Chuanxi Sun⁵  Gerald H. Learn⁵  Katharine J. Bar⁵  Yalu Chen⁵  Hui Li⁵  Maria G. Salazar⁵  Joseph E. Schumacher⁵  Barton F. Haynes⁶  Martin Markowitz⁶  Bette T. Korber⁷  Alan S. Perelson⁸  Myron S. Cohen⁸  Elena E. Giorgi⁹  Charles B. Hicks⁹  Peter Hraber⁹  Joseph J. Eron⁹ 

[1] Aaron Diamond AIDS Research Center, New York, New York, United States of America;Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America;Department of Mathematics and Statistics, University of Massachusetts, Amherst, Massachusetts, United States of America;Department of Medicine, Duke University, Durham, North Carolina, United States of America;Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America;Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America;Nuclear and Particle Physics, Astrophysics and Cosmology (T-2), Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America;Santa Fe Institute, Santa Fe, New Mexico, United States of America;Theoretical Biology and Biophysics (T6), Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America

关键词: HIV-1;    Viral transmission;    infection;    Sequence analysis;    Men who have sex with men;    Viral replication;    Polymerase chain reaction;    DNA sequence analysis;    Sexually transmitted diseases;   

DOI  :  10.1371/journal.ppat.1000890

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY