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Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naive Patients
- Source :
- Scientific Reports, 7:4688. Nature Publishing Group, Scientific Reports, Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
- Publication Year :
- 2017
-
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.
- Subjects :
- 0301 basic medicine
Genotype
Science
Hepatitis C virus
Population
Viral quasispecies
Drug resistance
Biology
Viral Nonstructural Proteins
medicine.disease_cause
Antiviral Agents
Deep sequencing
Article
03 medical and health sciences
chemistry.chemical_compound
Plasma
Drug Resistance, Viral
medicine
Humans
education
NS5B
Hepatitis
education.field_of_study
Multidisciplinary
Sequence Analysis, RNA
High-Throughput Nucleotide Sequencing
Hepatitis C
Hepatitis C, Chronic
medicine.disease
Virology
Quasispecies
030104 developmental biology
chemistry
Liver
Immunology
Medicine
Subjects
Details
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports, 7:4688. Nature Publishing Group, Scientific Reports, Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
- Accession number :
- edsair.doi.dedup.....9f7a68f2f9a19e173009653e480be328