Detection of Natural Resistance Associated Substitutions by Ion Semiconductor Technology in HCV1b Positive, Direct Acting Antiviral Agents Naive Patients
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.
International journal of molecular sciences