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Title

Resistance of high fitness hepatitis C virus to lethal mutagenesis

AuthorsGallego, Isabel ; Gregori, Josep Maria; Soria, María Eugenia; García-Crespo, Carlos; García-Álvarez, Mónica; Gómez-González, Alfonso; Valiergue, Rosalie; Gómez, Jordi.; Esteban, Juan Ignacio; Quer, Josep; Domingo, Esteban ; Perales, Celia
Issue Date2018
PublisherElsevier
CitationVirology 523: 100- 109 (2018)
AbstractViral fitness quantifies the degree of virus adaptation to a given environment. How viral fitness can influence the mutant spectrum complexity of a viral quasispecies subjected to lethal mutagenesis has not been investigated. Here we document that two high fitness hepatitis C virus populations display higher resistance to the mutagenic nucleoside analogues favipiravir and ribavirin than their parental, low fitness HCV. All populations, however, exhibited a mutation transition bias indicative of active mutagenesis. Resistance to the analogues was associated with a limited expansion of mutant spectrum complexity, as evidenced by several diversity indices used to characterize mutant spectra. The results are consistent with a replicative site-drug competition mechanism that was previously proposed for HCV fitness-associated resistance to non-mutagenic inhibitors. Other alternative, non-mutually exclusive mechanisms are considered. The results introduce viral fitness as a relevant parameter to evaluate the response of viruses to lethal mutagenesis, with implications for antiviral designs.
Publisher version (URL)http://dx.doi.org/10.1016/j.virol.2018.07.030
URIhttp://hdl.handle.net/10261/202326
DOIhttp://dx.doi.org/10.1016/j.virol.2018.07.030
Identifiersdoi: 10.1016/j.virol.2018.07.030
issn: 0042-6822
pmid: 30107298
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