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Fitness ranking of individual mutants drives patterns of epistatic interactions in HIV-1

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dc.contributor.author Martinez, Javier P.
dc.contributor.author Bocharov, Gennady A.
dc.contributor.author Ignatovich, Anna
dc.contributor.author Reiter, Jochen
dc.contributor.author Dittmar, Matthias T
dc.contributor.author Wain-Hobson, Simon
dc.contributor.author Meyerhans, Andreas
dc.date.accessioned 2015-04-29T09:17:24Z
dc.date.available 2015-04-29T09:17:24Z
dc.date.issued 2011
dc.identifier.citation Martinez JP, Bocharov G, Ignatovich A, Reiter J, Dittmar MT, Wain-Hobson S, Meyerhans A. Fitness ranking of individual mutants drives patterns of epistatic interactions in HIV-1. PLoS ONE. 2011;6(3):e18375. DOI: 10.1371/journal.pone.0018375
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10230/23496
dc.description.abstract Fitness interactions between mutations, referred to as epistasis, can strongly impact evolution. For RNA viruses and retroviruses with their high mutation rates, epistasis may be particularly important to overcome fitness losses due to the accumulation of deleterious mutations and thus could influence the frequency of mutants in a viral population. As human immunodeficiency virus type 1 (HIV-1) resistance to azidothymidine (AZT) requires selection of sequential mutations, it is a good system to study the impact of epistasis. Here we present a thorough analysis of a classical AZT-resistance pathway (the 41–215 cluster) of HIV-1 variants by fitness measurements in single round infection assays covering physiological drug concentrations ex vivo. The sign and value of epistasis varied and did not predict the epistatic effect on the mutant frequency. This complex behavior is explained by the fitness ranking of the variants that strongly depends on environmental factors, i.e., the presence and absence of drugs and the host cells used. Although some interactions compensate fitness losses, the observed small effect on the relative mutant frequencies suggests that epistasis might be inefficient as a buffering mechanism for fitness losses in vivo. While the use of epistasis-based hypotheses to make general assumptions on the evolutionary dynamics of viral populations is appealing, our data caution their interpretation without further knowledge on the characteristics of the viral mutant spectrum under different environmental conditions
dc.description.sponsorship This work was supported by grants from the Deutsche Forschungsgemeinschaft, the Deutsche Akademische Austauschdienst (DAAD), and the Russian Foundation for Basic Research and by the Program of the Russian Academy of Sciences "Basic Research for Medicine". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PLoS ONE. 2011;6(3):e18375
dc.rights © 2011 Martínez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
dc.subject.other VIH (Virus)
dc.subject.other Evolució molecular
dc.title Fitness ranking of individual mutants drives patterns of epistatic interactions in HIV-1
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0018375
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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