Detection of Natural Resistance-Associated Substitutions by Ion Semiconductor Technology in HCV1b Positive, Direct-Acting Antiviral Agents-Naive Patients

作者：Marascio Nadia^*; Pavia Grazia; Strazzulla Alessio; Dierckx Tim; Cuypers Lize; Vrancken Bram; Barreca Giorgio Settimo; Mirante Teresa; Malanga Donatella; Oliveira Duarte Mendes; Vandamme Anne Mieke; Torti Carlo; Liberto Maria Carla; Foca Alfredo

来源：International Journal of Molecular Sciences, 2016, 17(9): 1416.

DOI：10.3390/ijms17091416

• hepatitis C virus 1b
• resistance-associated substitutions
• direct-acting antiviral agents
• deep-sequencing

Naturally occurring resistance-associated substitutions (RASs) can negatively impact the response to direct-acting antivirals (DAAs) agents-based therapies for hepatitis C virus (HCV) infection. Herein, we set out to characterize the RASs in the HCV1b genome from serum samples of DAA-naive patients in the context of the SINERGIE (South Italian Network for Rational Guidelines and International Epidemiology, 2014) project. We deep-sequenced the NS3/4A protease region of the viral population using the Ion Torrent Personal Genome Machine, and patient-specific majority rule consensus sequence summaries were constructed with a combination of freely available next generation sequencing data analysis software. We detected NS3/4A protease major and minor variants associated with resistance to boceprevir (V36L), telaprevir (V36L, I132V), simeprevir (V36L), and grazoprevir (V36L, V170I). Furthermore, we sequenced part of HCV NS5B polymerase using Sanger-sequencing and detected a natural RAS for dasabuvir (C316N). This mutation could be important for treatment strategies in cases of previous therapy failure.

• 出版日期2016-9
• 单位KU Leuven; 河北医科大学