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Basic Characteristics of Mutations
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Mutation Site
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T54S |
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Mutation Site Sentence
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We found nine PI-resistance-associated variants (V36A, T54S, V55I, Q80K, Q80R, V107I, I132V, D168E, M175L) in HCV-NS3 of 10 patients. |
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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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NS3 |
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Standardized Encoding Gene
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NS3
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Genotype/Subtype
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1 |
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Viral Reference
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AF009606;D90208
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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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Clinical and Epidemiological Correlations
|
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Clinical Information
|
Y |
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Treatment
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PI |
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Location
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Brazil |
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Literature Information
|
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PMID
|
26674563
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Title
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No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy
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Author
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Hoffmann L,Faffe DS,Lima JF,Capitanio TA,Cabral BC,Urmenyi TP,Coelho HS,Rondinelli E,Villela-Nogueira CA,Silva R
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Journal
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BBA clinical
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Journal Info
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2015 Jan 30;3:146-51
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Abstract
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Direct-acting antiviral (DAA)-based therapy is the new standard treatment for chronic hepatitis C virus (HCV) infection. However, protease inhibitor (PI)-resistant viral variants have been often described. This study aimed to examine HCV-NS3 protease variants at baseline and at 4 weeks under triple therapy. To this end, we analyzed the presence of variants in HCV-NS3 protease region from peripheral blood samples of 16 patients infected with HCV-1 at baseline and at 4 weeks of combined therapy with telaprevir, pegylated interferon, and ribavirin, using next-generation sequencing. Several variants with synonymous and non-synonymous amino acid substitutions were detected at both time points. Variants detected at low frequency corresponded to 74% (HCV-1a) and 35% (HCV-1b) of non-synonymous substitutions. We found nine PI-resistance-associated variants (V36A, T54S, V55I, Q80K, Q80R, V107I, I132V, D168E, M175L) in HCV-NS3 of 10 patients. There was no correspondence of resistance-associated variant profile between baseline and at 4 weeks. Moreover, these resistance variants at baseline and short-term treatment are not good predictors of outcome under triple therapy. Our study also shows a large number of others minor and major non-synonymous variants in HCV-NS3 early in telaprevir-based therapy that can be important for further drug resistance association studies with newly developed PI agents.
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Sequence Data
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-
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