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Basic Characteristics of Mutations
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Mutation Site
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L31M |
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Mutation Site Sentence
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An NS5A polymorphism, L31M, was detected in all cases of g2a infection, and L31M+R353K in individuals that failed treatment. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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NS5A |
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Standardized Encoding Gene
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NS5A
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Genotype/Subtype
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2a |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HCV Infection
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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- |
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Location
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UK |
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Literature Information
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PMID
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36016300
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Title
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Characterisation of a Hepatitis C Virus Subtype 2a Cluster in Scottish PWID with a Suboptimal Response to Glecaprevir/Pibrentasvir Treatment
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Author
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Shah R,Barclay ST,Peters ES,Fox R,Gunson R,Bradley-Stewart A,Shepherd SJ,MacLean A,Tong L,van Vliet VJE,Ngan Chiu Bong M,Filipe A,Thomson EC,Davis C
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Journal
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Viruses
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Journal Info
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2022 Jul 29;14(8):1678
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Abstract
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Direct-acting antivirals (DAAs) have revolutionised the treatment of Hepatitis C virus (HCV), allowing the World Health Organisation (WHO) to set a target of eliminating HCV by 2030. In this study we aimed to investigate glecaprevir and pibrentasvir (GP) treatment outcomes in a cohort of patients with genotype 2a infection. METHODS: Clinical data and plasma samples were collected in NHS Greater Glasgow & Clyde. Next generation whole genome sequencing and replicon assays were carried out at the MRC-University of Glasgow Centre for Virus Research. RESULTS: 132 cases infected with genotype 2a HCV were identified. The SVR rate for this group was 91% (112/123) following treatment with GP. An NS5A polymorphism, L31M, was detected in all cases of g2a infection, and L31M+R353K in individuals that failed treatment. The results showed that R353K was present in 90% of individuals in the Glasgow genotype 2a phylogenetic cluster but in less than 5% of all HCV subtype 2a published sequences. In vitro efficacy of pibrentasvir against sub-genomic replicon constructs containing these mutations showed a 2-fold increase in IC(50) compared to wildtype. CONCLUSION: This study describes a cluster of HCV genotype 2a infection associated with a lower-than-expected SVR rate following GP treatment in association with the NS5A mutations L31M+R353K.
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Sequence Data
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OP022902-OP022921
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