|
Basic Characteristics of Mutations
|
|
Mutation Site
|
A30K |
|
Mutation Site Sentence
|
Due to the overlapping incidence of A30K, 96% of GT3b isolates had NS5A RASs combination A30K + L31M, which confers high levels of resistance to most NS5A inhibitors. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
NS5A |
|
Standardized Encoding Gene
|
NS5A
|
|
Genotype/Subtype
|
3b |
|
Viral Reference
|
AJ238799;AB047640;HQ912953;D49374;AY859526
|
|
Functional Impact and Mechanisms
|
|
Disease
|
HCV Infection
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
daclatasvir;elbasvir;ledipasvir;pibrentasvir;velpatasvir |
|
Location
|
China |
|
Literature Information
|
|
PMID
|
30941111
|
|
Title
|
Subtype-Specific Prevalence of Hepatitis C Virus NS5A Resistance Associated Substitutions in Mainland China
|
|
Author
|
Lu J,Feng Y,Chen L,Zeng Z,Liu X,Cai W,Wang H,Guo X,Zhou H,Tao W,Xie Q
|
|
Journal
|
Frontiers in microbiology
|
|
Journal Info
|
2019 Mar 19;10:535
|
|
Abstract
|
Resistance associated substitutions (RASs) can reduce the efficacy of direct-acting antiviral agents (DAAs) targeting hepatitis C virus (HCV) and lead to treatment failure. Clinical data of HCV NS5A RASs prevalence are limited in China and need to be investigated. A total of 878 unique patient samples with different genotypes (GT) (1b: n = 489, 2a: n = 203, 3a: n = 60, 3b: n = 78, 6a: n = 48) were collected from around mainland China by KingMed Laboratory and analyzed for NS5A RASs distribution by Sanger sequencing. Phylogeographic analyses based on NS5A domain 1 sequences indicated circulation of both locally and nationally epidemic strains. Relatively high frequency of Y93H (14.1%) was only detected in GT1b but not in other subtypes. High frequency of L31M was found in both GT2a (95.6%) and GT3b (98.7%) sequences. Due to the overlapping incidence of A30K, 96% of GT3b isolates had NS5A RASs combination A30K + L31M, which confers high levels of resistance to most NS5A inhibitors. No RASs were detected in GT6a strains. Meanwhile, baseline NS5A RASs fingerprints were also evaluated in 185 DAA treatment-naive GT1b patients with next generation sequencing method. Patients presenting with Y93H had statistically higher entropy of HCV NS5A sequences. Taken together, subtype-specific distribution patterns of NS5A RASs were observed. GT1b patients with higher HCV complexity tend to have a greater chance of Y93H presence, while GT3b patients are naturally resistant to current NS5A inhibitors and their treatment may pose a challenge to real-world DAA application.
|
|
Sequence Data
|
MK255325- MK256202;SAMN10458261-SAMN10458445
|