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Article

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

1
Department of Health Sciences, Institute of Microbiology, School of Medicine, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy
2
Katholieke Universiteit (KU) Leuven–University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, 3000 Leuven, Belgium
3
Department of Medical and Surgical Sciences, Unit of Infectious and Tropical Diseases, School of Medicine, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy
4
Centro di Servizio Interdipartimentale (CIS)-Genomica funzionale e Patologia Molecolare, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy
5
Department of Experimental and Clinical Medicine, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy
6
Center for Global Health and Tropical Medicine, Institute for Hygiene and Tropical Medicine, University Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisbon, Portugal
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Int. J. Mol. Sci. 2016, 17(9), 1416; https://doi.org/10.3390/ijms17091416
Received: 7 July 2016 / Revised: 17 August 2016 / Accepted: 22 August 2016 / Published: 27 August 2016
(This article belongs to the Special Issue Precision Medicine—From Bench to Bedside)
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-naïve 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. View Full-Text
Keywords: hepatitis C virus 1b; resistance-associated substitutions; direct-acting antiviral agents; deep-sequencing hepatitis C virus 1b; resistance-associated substitutions; direct-acting antiviral agents; deep-sequencing
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MDPI and ACS Style

Marascio, N.; Pavia, G.; Strazzulla, A.; Dierckx, T.; Cuypers, L.; Vrancken, B.; Barreca, G.S.; Mirante, T.; Malanga, D.; Oliveira, D.M.; Vandamme, A.-M.; Torti, C.; Liberto, M.C.; Focà, A.; The SINERGIE-UMG Study Group. Detection of Natural Resistance-Associated Substitutions by Ion Semiconductor Technology in HCV1b Positive, Direct-Acting Antiviral Agents-Naïve Patients. Int. J. Mol. Sci. 2016, 17, 1416. https://doi.org/10.3390/ijms17091416

AMA Style

Marascio N, Pavia G, Strazzulla A, Dierckx T, Cuypers L, Vrancken B, Barreca GS, Mirante T, Malanga D, Oliveira DM, Vandamme A-M, Torti C, Liberto MC, Focà A, The SINERGIE-UMG Study Group. Detection of Natural Resistance-Associated Substitutions by Ion Semiconductor Technology in HCV1b Positive, Direct-Acting Antiviral Agents-Naïve Patients. International Journal of Molecular Sciences. 2016; 17(9):1416. https://doi.org/10.3390/ijms17091416

Chicago/Turabian Style

Marascio, Nadia; Pavia, Grazia; Strazzulla, Alessio; Dierckx, Tim; Cuypers, Lize; Vrancken, Bram; Barreca, Giorgio S.; Mirante, Teresa; Malanga, Donatella; Oliveira, Duarte M.; Vandamme, Anne-Mieke; Torti, Carlo; Liberto, Maria C.; Focà, Alfredo; The SINERGIE-UMG Study Group. 2016. "Detection of Natural Resistance-Associated Substitutions by Ion Semiconductor Technology in HCV1b Positive, Direct-Acting Antiviral Agents-Naïve Patients" Int. J. Mol. Sci. 17, no. 9: 1416. https://doi.org/10.3390/ijms17091416

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