Selection bias at the heterosexual HIV-1 transmission bottleneck

Jonathan M. Carlson(Microsoft (United States)), Malinda Schaefer(Emory University), Daniela C. Mónaco(Emory University), Rebecca Batorsky(Ragon Institute of MGH, MIT and Harvard), Daniel T. Claiborne(Emory University), Jessica Prince(Emory University), Martin J. Deymier(Emory University), Zachary Ende(Emory University), Nichole R. Klatt(Emory University), Charles E. DeZiel(Microsoft (United States)), Tien-Ho Lin(Microsoft (United States)), Jian Peng(Microsoft (United States)), Aaron Seese(Ragon Institute of MGH, MIT and Harvard), Roger Shapiro(Beth Israel Deaconess Medical Center), John Frater(National Institute for Health and Care Research), Thumbi Ndung’u(Centre for the AIDS Programme of Research in South Africa), Jianming Tang(University of Alabama at Birmingham), Paul Goepfert(University of Alabama at Birmingham), Jill Gilmour(International AIDS Vaccine Initiative), Matt A. Price(International AIDS Vaccine Initiative), William Kilembe(Rwanda Zambia HIV Research Group), David Heckerman(Microsoft (United States)), Philip Goulder(Centre for the AIDS Programme of Research in South Africa), Todd M. Allen(Emory University), Susan Allen(Microsoft (United States)), Eric Hunter(Emory University)
Science
July 10, 2014
Cited by 268Open Access
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Abstract

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.


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