title: HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck.
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.
authors.affiliation: Microsoft Research, Redmond, WA 98052, USA. carlson@microsoft.com ehunte4@emory.edu.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Carlson
authors.affiliation: Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Malinda
authors.initials: M
authors.lastname: Schaefer
authors.affiliation: Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Monaco
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Batorsky
authors.affiliation: Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Claiborne
authors.affiliation: Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Prince
authors.affiliation: Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Deymier
authors.affiliation: Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Ende
authors.affiliation: Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.affiliation: Microsoft Research, Redmond, WA 98052, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: DeZiel
authors.affiliation: Microsoft Research, Redmond, WA 98052, USA.
authors.forename: Tien-Ho
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Microsoft Research, Redmond, WA 98052, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Peng
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Seese
authors.affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Shapiro
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 7BN, UK. National Institute of Health Research, Oxford Biomedical Research Centre, Oxford OX3 7LE, UK. Oxford Martin School, University of Oxford, Oxford OX1 3BD, UK.
authors.forename: John
authors.initials: J
authors.lastname: Frater
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa. Max Planck Institute for Infection Biology, D-10117 Berlin, Germany.
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Goepfert
authors.affiliation: International AIDS Vaccine Initiative, London SW10 9NH, UK. Imperial College of Science Technology and Medicine, London SW10 9NH, UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.affiliation: International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94105, USA.
authors.forename: Matt A
authors.initials: MA
authors.lastname: Price
authors.affiliation: Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia.
authors.forename: William
authors.initials: W
authors.lastname: Kilembe
authors.affiliation: Microsoft Research, Los Angeles, CA 98117, USA.
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.affiliation: Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.affiliation: International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Microsoft Research, Los Angeles, CA 98117, USA. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.affiliation: Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. carlson@microsoft.com ehunte4@emory.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
mesh_terms: D000595:Amino Acid Sequence; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D018562:Disease Transmission, Infectious / Q000706:statistics & numerical data; D005260:Female; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics*; D020010:Heterosexuality; D059014:High-Throughput Nucleotide Sequencing; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D015233:Models, Statistical; D008969:Molecular Sequence Data; D017354:Point Mutation; D012307:Risk Factors; D012641:Selection, Genetic; D019562:Viral Load
chemical_list: D054298:Human Immunodeficiency Virus Proteins