Scientists have shown that HIV faces a genetic "bottleneck" when the virus is transmitted heterosexually from one person to another, by way of the genital mucosa. The results, published January 23 in the open-access journal PLoS Pathogens, explain why prior infection by other sexually-transmitted diseases (STDs) makes individuals more susceptible to HIV infection.
The team of researchers, lead by Eric Hunter of Emory University, identified 20 heterosexual couples soon after infection occurred and obtained viral genetic sequences from both partners. They examined the most variable region of the virus' env gene, which encodes a protein forming the outer coat of the virus. Approximately 90% of the couple recipients were found to be infected by a single viral variant of HIV-1. However, that variant was not the same in each case.
For comparison, the researchers also analyzed a group of newly infected individuals who were infected by someone other than their spouse. This group showed more variety in viral sequences, with 3 out of 7 individuals infected by multiple variants. Overall, out of 42 newly infected people studied to date, all five infected by multiple viral variants had evidence of genital inflammation or ulceration.
In these cases, it appears that the bottleneck was enlarged due to the disruption of normally protective mucosal barriers by STDs. These findings suggest that the genital mucosa provides a natural barrier to infection by multiple genetic variants of HIV-1 that can be lowered by inflammatory genital infections.
To identify newly infected individuals, the team collaborated with public health programs directed by Susan Allen of Emory's Rollins School of Public Health that enroll thousands of heterosexual couples with one HIV-positive partner in Rwanda and Zambia.
The research was funded by grants from the National Institutes of Health, the Bill & Melinda Gates Foundation Grand Challenges Program and the International AIDS Vaccine Initiative.
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CITATION: Haaland RE, Hawkins PA, Salazar-Gonzalez J, Johnson A, Tichacek A, et al. (2009) Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual Transmission of Subtype A and C HIV-1. PLoS Pathog 5(1): e1000274. doi:10.1371/journal.ppat.1000274
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