|
Basic Characteristics of Mutations
|
|
Mutation Site
|
C316N |
|
Mutation Site Sentence
|
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. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
NS5B |
|
Standardized Encoding Gene
|
NS5B
|
|
Genotype/Subtype
|
1b |
|
Viral Reference
|
AJ238799
|
|
Functional Impact and Mechanisms
|
|
Disease
|
HCV Infection
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
Y |
|
Treatment
|
non- nucleoside inhibitors |
|
Location
|
Netherlands |
|
Literature Information
|
|
PMID
|
28680115
|
|
Title
|
Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naive Patients
|
|
Author
|
Raj VS,Hundie GB,Schurch AC,Smits SL,Pas SD,Le Pogam S,Janssen HLA,de Knegt RJ,Osterhaus ADME,Najera I,Boucher CA,Haagmans BL
|
|
Journal
|
Scientific reports
|
|
Journal Info
|
2017 Jul 5;7(1):4688
|
|
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-naive patients. Population-based sequencing and 454 deep sequencing of NS5B gene were performed on plasma and liver samples obtained from 18 treatment- naive 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 naive 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.
|
|
Sequence Data
|
KF730703-KF730738
|