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

• Published in: PLoS pathogens Vol. 6; no. 5; p. e1000890
• Main Authors: Li, Hui, Bar, Katharine J., Wang, Shuyi, Decker, Julie M., Chen, Yalu, Sun, Chuanxi, Salazar-Gonzalez, Jesus F., Salazar, Maria G., Learn, Gerald H., Morgan, Charity J., Schumacher, Joseph E., Hraber, Peter, Giorgi, Elena E., Bhattacharya, Tanmoy, Korber, Bette T., Perelson, Alan S., Eron, Joseph J., Cohen, Myron S., Hicks, Charles B., Haynes, Barton F., Markowitz, Martin, Keele, Brandon F., Hahn, Beatrice H., Shaw, George M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2010; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Acquisitions & mergers; AIDS; BASIC BIOLOGICAL SCIENCES; Cloning; Development and progression; Disease Outbreaks - statistics & numerical data; env Gene Products, Human Immunodeficiency Virus - genetics; Evolution; Evolution, Molecular; Gays; Genetic Variation; Genome, Viral; Genomes; genomics; Heterosexuality - statistics & numerical data; HIV; HIV infection; HIV Infections - epidemiology; HIV Infections - prevention & control; HIV Infections - transmission; HIV-1; HIV-1 - genetics; HIV-1 - growth & development; HIV-1 - pathogenicity; Homosexuality, Male - statistics & numerical data; Host-virus relationships; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Infections; Infectious Diseases/HIV Infection and AIDS; Infectious Diseases/Sexually Transmitted Diseases; Male; medical risk factors; men who have sex with men; Models, Genetic; Physiological aspects; Plasma; polymerase chain reaction; Prevention; Recombination, Genetic - genetics; Risk Factors; Sexual Behavior - statistics & numerical data; sexually transmitted diseases; Studies; viral replication; viral transmission and infection; Virology; Virology/Animal Models of Infection; Virology/Host Invasion and Cell Entry; Virology/Immune Evasion; Virology/Immunodeficiency Viruses; Virology/Vaccines; Virology/Virus Evolution and Symbiosis; Virulence; Viruses; United States
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000890

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.