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Comprehensive Characterization of the Transmitted/Founder env Genes From a Single MSM Cohort in China
Yue Chen1, Ning Li, Tong Zhang
1*Duke Human Vaccine Institute, Duke University, Durham, NC; †Department of Medicine, Duke University, Durham, NC; ‡Beijing You'an Hospital, Capital Medical University, Beijing, China; §Beijing Center for Disease Control and Prevention, Beijing, China; ‖Shanghai Public Health Clinical Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China; ¶National Engineering Laboratory For AIDS Vaccine, College of Life Science, Jilin University, Changchun, China; #Department of Immunology, Chelsea and Westminster Hospital, Imperial College London, London, United Kingdom; and **Department of Surgery, Duke University, Durham, NC.
Background:
The men having sex with men (MSM) population has become one of the major risk groups for HIV-1 infection in China. However, the epidemiological patterns, function of the env genes, and autologous and heterologous neutralization activity in the same MSM population have not been systematically characterized.
Methods:
The env gene sequences were obtained by the single genome amplification. The time to the most recent common ancestor was estimated for each genotype using the Bayesian Markov Chain Monte Carlo approach. Coreceptor usage was determined in NP-2 cells. Neutralization was analyzed using Env pseudoviruses in TZM-bl cells.
Results:
We have obtained 547 full-length env gene sequences by single genome amplification from 30 acute/early HIV-1--infected individuals in the Beijing MSM cohort. Three genotypes (subtype B, CRF01_AE, and CRF07_BC) were identified and 20% of the individuals were infected with multiple transmitted/founder (T/F) viruses. The tight clusters of the MSM sequences regardless of geographic origins indicated nearly exclusive transmission within the MSM population and limited number of introductions. The time to the most recent common ancestor for each genotype was 10-15 years after each was first introduced in China. Disparate preferences for coreceptor usages among 3 genotypes might lead to the changes in percentage of different genotypes in the MSM population over time. The genotype-matched and genotype-mismatched neutralization activity varied among the 3 genotypes.
Conclusions:
The identification of unique characteristics for transmission, coreceptor usage, neutralization profile, and epidemic patterns of HIV-1 is critical for the better understanding of transmission mechanisms, development of preventive strategies, and evaluation of vaccine efficacy in the MSM population in China.
Insights
HIV-1 transmission in China
Area of Science:
- Virology
- Epidemiology
- Immunology
Background:
- Men who have sex with men (MSM) are a key risk group for HIV-1 in China.
- Epidemiological patterns, env gene function, and neutralization activity in this population require systematic characterization.
Purpose of the Study:
- To characterize HIV-1 env gene sequences, transmission dynamics, coreceptor usage, and neutralization profiles within the Beijing MSM cohort.
- To understand the epidemic patterns of HIV-1 in this specific population.
Main Methods:
- Single genome amplification of 547 full-length env gene sequences from 30 individuals.
- Bayesian Markov Chain Monte Carlo for estimating the time to the most recent common ancestor.
- Coreceptor usage and neutralization activity assays using cell lines and pseudoviruses.
Main Results:
- Identified three genotypes (B, CRF01_AE, CRF07_BC); 20% of individuals had multiple transmitted/founder viruses.
- Sequence clustering indicated transmission primarily within the MSM population with limited introductions.
- Disparate coreceptor usage and varying neutralization activity observed among genotypes.
Conclusions:
- Understanding unique transmission, coreceptor usage, and neutralization characteristics of HIV-1 in Chinese MSM is crucial.
- This knowledge aids in developing better prevention strategies and evaluating vaccine efficacy.
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