Journal Article

Selection bias at the heterosexual HIV-1 transmission bottleneck

Goepfert, Paul, Shapiro, Roger, Prince, Jessica, Carlson, Jonathan M., Price, Matt A., Allen, Susan, Deymier, Martin J., Goulder, Philip J.R., Klatt, Nichole R., DeZiel, Charles E., Allen, Todd M., Hunter, Eric, Monaco, Daniela C., Ndung'u, Thumbi, Peng, Jian, Batorsky, Rebecca, Seese, Aaron M., Heckerman, David, Tang, Jianming, Kilembe, William, Lin, Tien-Ho, Schaefer, Malinda, Frater, John, Ende, Zachary S., Gilmour, Jill, Claiborne, Daniel T.

2014

Overview

Although you might not think it, it's hard to catch HIV. Less than 1% of unprotected sexual exposures result in infection. What then leads to transmission? Carlson et al. determined the amino acid sequence of viruses infecting 137 Zambian heterosexual couples in which one partner infected the other (see the Perspective by Joseph and Swanstrom). The authors then used statistical modeling and found that transmitted viruses are typically the most evolutionarily fit. That is, compared to other viral variants in the infected person, the transmitted virus most closely matches the most common viral sequence found in the Zambian population. Science , this issue 10.1126/science.1254031 ; see also p. 136 An analysis of discordant couples reveals that transmitted HIV-1 viruses are typically the most evolutionarily fit. [Also see Perspective by Joseph and Swanstrom ] Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked transmission pairs, the amino acid sequences encoded by non-envelope genes of viruses in both partners and demonstrate a selection bias for transmission of residues that are predicted to confer increased in vivo fitness on viruses in the newly infected, immunologically naïve recipient. Although tempered by transmission risk factors, such as donor viral load, genital inflammation, and recipient gender, this selection bias provides an overall transmission advantage for viral quasispecies that are dominated by viruses with high in vivo fitness. Thus, preventative or therapeutic approaches that even marginally reduce viral fitness may lower the overall transmission rates and offer long-term benefits even upon successful transmission.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: amino acid sequences / Amino acids / Bias / Couples / Donors / Exposure / Females / Genetic variance / Human immunodeficiency virus / Human immunodeficiency virus 1 / Lentivirus / Males / Modelling / RESEARCH ARTICLE SUMMARY / Risk factors / Sexual Orientation / Sexually transmitted diseases / Statistical Bias / Statistical models / STD / Stochastic processes / Viruses