High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men
Autor: | Shuyi Wang, Gerald H. Learn, Myron S. Cohen, Julie M. Decker, Katharine J. Bar, Peter T. Hraber, Charles B. Hicks, Jesus F. Salazar-Gonzalez, Bette T. Korber, Alan S. Perelson, Joseph E. Schumacher, Joseph J. Eron, Chuanxi Sun, Elena E. Giorgi, H Li, George M. Shaw, Yalu Chen, Tanmoy Bhattacharya, Brandon F. Keele, Barton F. Haynes, Beatrice H. Hahn, Maria G. Salazar, Charity J. Morgan, Martin Markowitz |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Male
viruses HIV Infections Genome Disease Outbreaks Men who have sex with men Risk Factors lcsh:QH301-705.5 Virology/Vaccines Recombination Genetic Genetics 0303 health sciences Virulence Transmission (medicine) env Gene Products Human Immunodeficiency Virus Infectious Diseases/HIV Infection and AIDS Virology/Virus Evolution and Symbiosis 3. Good health Virology/Immunodeficiency Viruses Viral evolution Virology/Animal Models of Infection Research Article lcsh:Immunologic diseases. Allergy Sexual Behavior Immunology Viremia Context (language use) Genome Viral Virology/Immune Evasion Biology Microbiology Virus Evolution Molecular 03 medical and health sciences Virology Infectious Diseases/Sexually Transmitted Diseases medicine Humans Homosexuality Male Heterosexuality Molecular Biology 030304 developmental biology Models Genetic 030306 microbiology Genetic Variation Virology/Host Invasion and Cell Entry medicine.disease Viral replication lcsh:Biology (General) HIV-1 Parasitology lcsh:RC581-607 |
Zdroj: | PLoS Pathogens, Vol 6, Iss 5, p e1000890 (2010) PLoS Pathogens |
ISSN: | 1553-7374 1553-7366 |
Popis: | 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. Author Summary Understanding the biology of sexual transmission of HIV-1 could contribute importantly to the development of effective prevention measures. However, different routes of virus transmission (vaginal, rectal, penile or oral) and inaccessibility of tissues at or near the time of virus transmission make this goal elusive. Here, we apply single genome amplification and sequencing of plasma HIV-1 and a model of random virus evolution to a cohort of acutely infected men who have sex with men (MSM) and find that MSM are twice as likely as heterosexuals to become infected by multiple viruses as opposed to a single virus. Some MSM subjects were infected by as many as 7 to 10 or more genetically distinct viruses as a consequence of a single exposure event. We go on to molecularly clone the first full-length transmitted/founder subtype B HIV-1 virus and show that it is highly replicative in human CD4+ T-cells but not macrophages. Our study provides the first comparative, quantitative analysis of the multiplicity of HIV-1 infection in the two primary risk groups—MSM and heterosexuals—driving the global pandemic, and we discuss the implications of the findings to HIV-1 vaccine development and prevention research. |
Databáze: | OpenAIRE |
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