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Int J Mol Sci. 2016 Aug 27;17(9). pii: E1416. doi: 10.3390/ijms17091416.

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

Author information

1
Department of Health Sciences, Institute of Microbiology, School of Medicine, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy. nadiamarascio@gmail.com.
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. nadiamarascio@gmail.com.
3
Department of Health Sciences, Institute of Microbiology, School of Medicine, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy. grazia_pavia@libero.it.
4
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. alessiostrazzulla@yahoo.it.
5
Katholieke Universiteit (KU) Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, 3000 Leuven, Belgium. tim.dierckx@kuleuven.be.
6
Katholieke Universiteit (KU) Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, 3000 Leuven, Belgium. lize.cuypers@kuleuven.be.
7
Katholieke Universiteit (KU) Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, 3000 Leuven, Belgium. bram.vrancken@kuleuven.be.
8
Department of Health Sciences, Institute of Microbiology, School of Medicine, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy. gbarreca@unicz.it.
9
Centro di Servizio Interdipartimentale (CIS)-Genomica funzionale e Patologia Molecolare, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy. teresa87@tiscalinet.it.
10
Department of Experimental and Clinical Medicine, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy. malanga@unicz.it.
11
Department of Experimental and Clinical Medicine, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy. oliveira@unicz.it.
12
Katholieke Universiteit (KU) Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, 3000 Leuven, Belgium. annemie.vandamme@uzleuven.be.
13
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. annemie.vandamme@uzleuven.be.
14
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. torti@unicz.it.
15
Department of Health Sciences, Institute of Microbiology, School of Medicine, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy. mliberto@unicz.it.
16
Department of Health Sciences, Institute of Microbiology, School of Medicine, University of Magna Graecia, Viale Europa, Germaneto, 88100 Catanzaro, Italy. alfredofoca@gmail.com.

Abstract

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.

KEYWORDS:

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

PMID:
27618896
PMCID:
PMC5037695
DOI:
10.3390/ijms17091416
[Indexed for MEDLINE]
Free PMC Article

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