|
Basic Characteristics of Mutations
|
|
Mutation Site
|
I280V |
|
Mutation Site Sentence
|
In genotype 1b, resistance mutations in NS5A (L28V, L31M, Q54H, Y93H and I280V) were observed in 16/30 (53.3%) patients, while resistance mutations in NS5B (L159F, V321I, C316N, M426L, Y452H, R465G and V499A) were observed in 27/30 (90%) patients. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
NS5A |
|
Standardized Encoding Gene
|
NS5A
|
|
Genotype/Subtype
|
1b |
|
Viral Reference
|
AY045702
|
|
Functional Impact and Mechanisms
|
|
Disease
|
HCV Infection
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
Y |
|
Treatment
|
Daclatasvir;Samatasvir;Ledipasvir;GSK805 |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
24341898
|
|
Title
|
Naturally occurring resistance mutations to inhibitors of HCV NS5A region and NS5B polymerase in DAA treatment-naive patients
|
|
Author
|
Paolucci S,Fiorina L,Mariani B,Gulminetti R,Novati S,Barbarini G,Bruno R,Baldanti F
|
|
Journal
|
Virology journal
|
|
Journal Info
|
2013 Dec 17;10:355
|
|
Abstract
|
BACKGROUND: Direct-acting antiviral (DAA) agents target HCV proteins; some of these have already been approved for the treatment of HCV infection, while others are in development. However, selection of DAA-resistant viral variants may hamper treatment. The aim of this study was to illustrate potential natural DAA-resistance mutations in the HCV NS5A and NS5B regions of HCV genotypes 1a and 1b from DAA-naive patients. METHODS: Direct sequencing of HCV NS5A and NS5B regions was performed in 32 patients infected with HCV genotype 1a and 30 patients infected with HCV genotype 1b; all subjects were naive to DAAs. RESULTS: In genotype 1a strains, resistance mutations in NS5A (M28V, L31M and H58P) were observed in 4/32 (12.5%) patients, and resistance mutations in NS5B (V321I, M426L, Y448H, Y452H) were observed in 4/32 (12.5%) patients. In genotype 1b, resistance mutations in NS5A (L28V, L31M, Q54H, Y93H and I280V) were observed in 16/30 (53.3%) patients, while resistance mutations in NS5B (L159F, V321I, C316N, M426L, Y452H, R465G and V499A) were observed in 27/30 (90%) patients. CONCLUSIONS: Mutations conferring DAA resistance were detected in NS5A and NS5B of HCV genotypes 1a and 1b from DAA-naive patients. Although some mutations confer only a low level of resistance, the presence at baseline of mutated HCV variants should be taken into consideration in the context of DAA therapy.
|
|
Sequence Data
|
KF667756 - KF667879
|
|
|