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E-mail Address : ehunte4@emory.edu ; carlson@microsoft.com

Jonathan M. Carlson and Malinda Schaefer contributed equally to this manuscript

The investigators thank all the volunteers in Zambia who participated in this study and all the staff at the Zambia Emory HIV Research Project in Lusaka who made this study possible.

The investigators would like to thank Jon Allen, and Mackenzie Hurlston for technical assistance and sample management, Paul Farmer, Ph.D. for database design and management, and Ilene Brill, Kristin Wall, Xuelin Li, Christoph Lippert, Nicolo Fusi, Jennifer Listgarten, and Zabrina Brumme for helpful discussions.

JP, DTC and Malinda Schaefer were supported in part by Action Cycling Fellowships.

TN was supported by the International AIDS Vaccine Initiative, the South African Department of Science and Technology and the National Research Foundation through the South Africa Research Chairs Initiative, by an International Early Career Scientist award from the Howard Hughes Medical Institute and by the Victor Daitz Foundation.

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Research Funding:

This study was funded by R01 AI64060 and R37 AI51231 (EH) from the National Institutes of Health, and the International AIDS Vaccine Initiative (to SAA), and made possible in part by the generous support of the American people through the United States Agency for International Development (USAID).

This work was also supported, in part, by the Virology Core at the Emory Center for AIDS Research (Grant P30 AI050409); the Yerkes National Primate Research Center base grant (2P51RR000165-51) through the National Center for Research Resources P51RR165 and by the Office of Research Infrastructure Programs/OD P51OD11132; NIH NIAID grants P01-AI074415 (TMA), U01 AI 66454 (RS), T32-AI007387 (RB), and RO1 AI046995 (PG), and the Wellcome Trust (PG).

Keywords:

  • HIV-1 transmission
  • Heterosexual
  • Selection bias

Heterosexual Transmission of Subtype C HIV-1 Selects Consensus-Like Variants without Increased Replicative Capacity or Interferon-α Resistance

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Journal Title:

Science

Volume:

Volume 11, Number 9

Publisher:

, Pages e1005154-e1005154

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Heterosexual transmission of HIV-1 is characterized by a genetic bottleneck that selects a single viral variant, the transmitted/founder (TF), during most transmission events. To assess viral characteristics influencing HIV-1 transmission, we sequenced 167 near full-length viral genomes and generated 40 infectious molecular clones (IMC) including TF variants and multiple non-transmitted (NT) HIV-1 subtype C variants from six linked heterosexual transmission pairs near the time of transmission. Consensus-like genomes sensitive to donor antibodies were selected for during transmission in these six transmission pairs. However, TF variants did not demonstrate increased viral fitness in terms of particle infectivity or viral replicative capacity in activated peripheral blood mononuclear cells (PBMC) and monocyte-derived dendritic cells (MDDC). In addition, resistance of the TF variant to the antiviral effects of interferon-α (IFN-α) was not significantly different from that of non-transmitted variants from the same transmission pair. Thus neither in vitro viral replicative capacity nor IFN-α resistance discriminated the transmission potential of viruses in the quasispecies of these chronically infected individuals. However, our findings support the hypothesis that within-host evolution of HIV-1 in response to adaptive immune responses reduces viral transmission potential.

Copyright information:

© 2014, American Association for the Advancement of Science

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