Resistance of high fitness hepatitis C virus to lethal mutagenesis

Isabel Gallego, Josep Gregori, María Eugenia Soria, Carlos García-Crespo, Mónica García-Álvarez, Alfonso Gómez-González, Rosalie Valiergue, Jordi Gómez, Juan Ignacio Esteban, Josep Quer, Esteban Domingo, Celia Perales

Research output: Contribution to journalArticleResearch

13 Citations (Scopus)

Abstract

© 2018 Elsevier Inc. Viral 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.
Original languageEnglish
Pages (from-to)100-109
JournalVirology
Volume523
DOIs
Publication statusPublished - 1 Oct 2018

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