@article{fb4ea884dff34179b920bb5f2f886f90,
title = "Evolution of HIV-1 within untreated individuals and at the population scale in Uganda",
abstract = "HIV-1 undergoes multiple rounds of error-prone replication between transmission events, resulting in diverse viral populations within and among individuals. In addition, the virus experiences different selective pressures at multiple levels: during the course of infection, at transmission, and among individuals. Disentangling how these evolutionary forces shape the evolution of the virus at the population scale is important for understanding pathogenesis, how drug- and immune-escape variants are likely to spread in populations, and the development of preventive vaccines. To address this, we deep-sequenced two regions of the HIV-1 genome (p24 and gp41) from 34 longitudinally-sampled untreated individuals from Rakai District in Uganda, infected with subtypes A, D, and inter-subtype recombinants. This dataset substantially increases the availability of HIV-1 sequence data that spans multiple years of untreated infection, in particular for different geographical regions and viral subtypes. In line with previous studies, we estimated an approximately five-fold faster rate of evolution at the within-host compared to the population scale for both synonymous and nonsynonymous substitutions, and for all subtypes. We determined the extent to which this mismatch in evolutionary rates can be explained by the evolution of the virus towards population-level consensus, or the transmission of viruses similar to those that establish infection within individuals. Our findings indicate that both processes are likely to be important.",
author = "Jayna Raghwani and Redd, {Andrew D.} and Longosz, {Andrew F.} and Wu, {Chieh Hsi} and David Serwadda and Craig Martens and Joseph Kagaayi and Nelson Sewankambo and Porcella, {Stephen F.} and Grabowski, {Mary K.} and Quinn, {Thomas C.} and Eller, {Michael A.} and Eller, {Leigh Anne} and Fred Wabwire-Mangen and Robb, {Merlin L.} and Christophe Fraser and Lythgoe, {Katrina A.}",
note = "Funding Information: JR and KAL were supported by The Wellcome Trust (https://wellcome.ac.uk/) and The Royal Society (https://royalsociety.org/) grant no. 107652/Z/15/Z (KAL). This study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, (https://www.nih.gov/) and by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD). CF was supported by the Bridging the Evolution and Epidemiology of HIV in Europe (BEEHIVE) study via a European Research Council Advanced Grant, grant number PBDR-339251 (https://erc.europa.eu/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank the participants and staff of the Rakai Community Cohort study. We would also like to thank Richard Neher and Philippe Lemey for their generous contributions, and the CIPRES Science Gateway [72 ]. Disclaimer Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70–25. Publisher Copyright: {\textcopyright} 2018, Public Library of Science. All rights reserved. https://creativecommons.org/publicdomain/zero/1.0/.",
year = "2018",
month = jul,
doi = "10.1371/journal.ppat.1007167",
language = "English (US)",
volume = "14",
journal = "PLoS pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "7",
}