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Abstract
Set-point viral load (SPVL), a common measure of human immunodeficiency virus (HIV)-1 virulence, is partially determined by viral genotype. Epidemiological evidence suggests that this viral property has been under stabilising selection, with a typical optimum for the virus between 104 and 105 copies of viral RNA per ml. Here we aimed to detect transmission fitness differences between viruses from individuals with different SPVLs directly from phylogenetic trees inferred from whole-genome sequences. We used the local branching index (LBI) as a proxy for transmission fitness. We found that LBI is more sensitive to differences in infectiousness than to differences in the duration of the infectious state. By analysing subtype-B samples from the Bridging the Evolution and Epidemiology of HIV in Europe project, we inferred a significant positive relationship between SPVL and LBI up to approximately 105 copies/ml, with some evidence for a peak around this value of SPVL. This is evidence of selection against low values of SPVL in HIV-1 subtype-B strains, likely related to lower infectiousness, and perhaps a peak in the transmission fitness in the expected range of SPVL. The less prominent signatures of selection against higher SPVL could be explained by an inherent limit of the method or the deployment of antiretroviral therapy.
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Details
1 Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford , Old Road Campus, Headington, Oxford OX3 7LF, UK
2 Centre for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, PSL Research University , Cedex 05, Paris 75231, France
3 European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus , Cambridge CB10 1SD, UK
4 Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, University of Amsterdam , Amsterdam, MB 1007, Netherlands
5 Stichting HIV Monitoring , Amsterdam, Amsterdam, AZ 1105, Netherlands
6 Wellcome Sanger Institute, Wellcome Genome Campus , Hinxton, Cambridge CB10 1SA, UK
7 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Solna, Stockholm 171 77, Sweden
8 Division for HIV and Other Retroviruses, Department of Infectious Diseases, Robert Koch Institute , Berlin 13353, Germany
9 School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne , Lausanne CH-1015, Switzerland
10 Department of Pathology, John Hopkins University , Baltimore, MD 21287, USA
11 Department of Infectious Disease Epidemiology, Robert Koch Institute , Berlin 13353, Germany
12 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich , Zurich CH-8091, Switzerland
13 Department of Infectious Diseases, Helsinki University Hospital , Helsinki FI-00029, Finland
14 Division of Intramural Research, NIAID, NIH , Baltimore, MD 21205, USA
15 INSERM CESP U1018, Université Paris Saclay , APHP, Service de Santé Publique, Hôpital de Bicêtre, Le Kremlin-Bicêtre 94270, France
16 Institute for Global Health, University College London , London WC1N 1EH, UK
17 Kymab Ltd , Babraham Research Campus, Cambridge CB22 3AT, UK