Increased replicative fitness can lead to decreased drug sensitivity of hepatitis C virus

Julie Sheldon, Nathan M. Beach, Elena Moreno, Isabel Gallego, David Piñeiro, Encarnación Martínez-Salas, Josep Gregori, Josep Quer, Juan Ignacio Esteban, Charles M. Rice, Esteban Domingo, Celia Peralesa

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)


© 2014, American Society for Microbiology. Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed partial resistance to alpha interferon (IFN-α), telaprevir, daclatasvir, cyclosporine, and ribavirin, despite no prior exposure to these drugs. Mutant spectrum analyses and kinetics of virus production in the absence and presence of drugs indicate that resistance is not due to the presence of drug resistance mutations in the mutant spectrum of the initial or passaged populations but to increased replicative fitness acquired during passage. Fitness increases did not alter host factors that lead to shutoff of general host cell protein synthesis and preferential translation of HCV RNA. The results imply that viral replicative fitness is a mechanism of multidrug resistance in HCV.
Original languageEnglish
Pages (from-to)12098-12111
JournalJournal of Virology
Issue number20
Publication statusPublished - 1 Jan 2014


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