Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naïve Patients

Abstract Current standard-of-care treatment of chronically infected hepatitis C virus (HCV) patients involves direct-acting antivirals (DAA). However, concerns exist regarding the emergence of drug -resistant variants and subsequent treatment failure. In this study, we investigate potential natural...

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Autores principales:	V. Stalin Raj, Gadissa Bedada Hundie, Anita C. Schürch, Saskia L. Smits, Suzan D. Pas, Sophie Le Pogam, Harry L. A. Janssen, Rob J. de Knegt, Albert D. M. E. Osterhaus, Isabel Najera, Charles A. Boucher, Bart L. Haagmans
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Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/406c4163dec244f4a42d839b533621dc
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spelling	oai:doaj.org-article:406c4163dec244f4a42d839b533621dc2021-12-02T15:04:57ZIdentification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naïve Patients10.1038/s41598-017-04931-y2045-2322https://doaj.org/article/406c4163dec244f4a42d839b533621dc2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04931-yhttps://doaj.org/toc/2045-2322Abstract Current standard-of-care treatment of chronically infected hepatitis C virus (HCV) patients involves direct-acting antivirals (DAA). However, concerns exist regarding the emergence of drug -resistant variants and subsequent treatment failure. In this study, we investigate potential natural drug-resistance mutations in the NS5B gene of HCV genotype 1b from treatment-naïve patients. Population-based sequencing and 454 deep sequencing of NS5B gene were performed on plasma and liver samples obtained from 18 treatment- naïve patients. The quasispecies distribution in plasma and liver samples showed a remarkable overlap in each patient. Although unique sequences in plasma or liver were observed, in the majority of cases the most dominant sequences were shown to be identical in both compartments. Neither in plasma nor in the liver codon changes were detected at position 282 that cause resistance to nucleos(t)ide analogues. However, in 10 patients the V321I change conferring resistance to nucleos(t)ide NS5B polymerase inhibitors and in 16 patients the C316N/Y/H non-nucleoside inhibitors were found mainly in liver samples. In conclusion, 454-deep sequencing of liver and plasma compartments in treatment naïve patients provides insight into viral quasispecies and the pre-existence of some drug-resistant variants in the liver, which are not necessarily present in plasma.V. Stalin RajGadissa Bedada HundieAnita C. SchürchSaskia L. SmitsSuzan D. PasSophie Le PogamHarry L. A. JanssenRob J. de KnegtAlbert D. M. E. OsterhausIsabel NajeraCharles A. BoucherBart L. HaagmansNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q V. Stalin Raj Gadissa Bedada Hundie Anita C. Schürch Saskia L. Smits Suzan D. Pas Sophie Le Pogam Harry L. A. Janssen Rob J. de Knegt Albert D. M. E. Osterhaus Isabel Najera Charles A. Boucher Bart L. Haagmans Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naïve Patients
description	Abstract Current standard-of-care treatment of chronically infected hepatitis C virus (HCV) patients involves direct-acting antivirals (DAA). However, concerns exist regarding the emergence of drug -resistant variants and subsequent treatment failure. In this study, we investigate potential natural drug-resistance mutations in the NS5B gene of HCV genotype 1b from treatment-naïve patients. Population-based sequencing and 454 deep sequencing of NS5B gene were performed on plasma and liver samples obtained from 18 treatment- naïve patients. The quasispecies distribution in plasma and liver samples showed a remarkable overlap in each patient. Although unique sequences in plasma or liver were observed, in the majority of cases the most dominant sequences were shown to be identical in both compartments. Neither in plasma nor in the liver codon changes were detected at position 282 that cause resistance to nucleos(t)ide analogues. However, in 10 patients the V321I change conferring resistance to nucleos(t)ide NS5B polymerase inhibitors and in 16 patients the C316N/Y/H non-nucleoside inhibitors were found mainly in liver samples. In conclusion, 454-deep sequencing of liver and plasma compartments in treatment naïve patients provides insight into viral quasispecies and the pre-existence of some drug-resistant variants in the liver, which are not necessarily present in plasma.
format	article
author	V. Stalin Raj Gadissa Bedada Hundie Anita C. Schürch Saskia L. Smits Suzan D. Pas Sophie Le Pogam Harry L. A. Janssen Rob J. de Knegt Albert D. M. E. Osterhaus Isabel Najera Charles A. Boucher Bart L. Haagmans
author_facet	V. Stalin Raj Gadissa Bedada Hundie Anita C. Schürch Saskia L. Smits Suzan D. Pas Sophie Le Pogam Harry L. A. Janssen Rob J. de Knegt Albert D. M. E. Osterhaus Isabel Najera Charles A. Boucher Bart L. Haagmans
author_sort	V. Stalin Raj
title	Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naïve Patients
title_short	Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naïve Patients
title_full	Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naïve Patients
title_fullStr	Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naïve Patients
title_full_unstemmed	Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naïve Patients
title_sort	identification of hcv resistant variants against direct acting antivirals in plasma and liver of treatment naïve patients
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/406c4163dec244f4a42d839b533621dc
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Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naïve Patients

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