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Basic Characteristics of Mutations
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Mutation Site
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R70Q |
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Mutation Site Sentence
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Substitution of R70Q/H alone is not enough to lead to resistance to therapy. |
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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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C |
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Standardized Encoding Gene
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Core
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Genotype/Subtype
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1b |
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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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Hepatitis C, Chronic
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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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PEG-IFNα;RBV |
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Location
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China |
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Literature Information
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PMID
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26684004
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Title
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Kinetic response of wild and mutant core codon 70 strains of HCV genotype 1b to pegylated interferon-alpha and ribavirin therapy
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Author
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Hu Z,Liu Y,Qiu L,Fan Z,Nie W,Liang S,Jin R
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Journal
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Virology journal
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Journal Info
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2015 Dec 18;12:220
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Abstract
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BACKGROUND: Amino acid (aa) 70 substitution (R70Q/H) in the core protein of hepatitis C virus (HCV) genotype 1b has been shown to be one of the key factors in determining resistance for pegylated interferon-alpha plus ribavirin combination therapy (PEG-IFNalpha/RBV). But the exact mechanisms remain unclear. The aim of this study was to investigate the dynamic response of wild and mutant core codon 70 strains to PEG-IFNalpha/RBV treatment. METHODS: One hundred twelve Chinese patients with chronic HCV 1b infection were enrolled and received a standard protocol of 48 weeks of PEG-IFNalpha/RBV therapy and 24 consecutive weeks of follow-up. Serial blood samples were obtained at pretreatment baseline, and again at weeks 2, 4, 8, 12, and 24 during therapy for the quantification of 70R and 70Q/H strains. Dynamic characteristics and association with early virological response (EVR), sustained virological response (SVR) and IL28B genotypes were analyzed. RESULTS: Of the 112 patients enrolled in this study, 93.8% (105/112) were infected with mixture of 70R and 70Q/H strains before treatment. The 70Q/H strain was dominant in 20.5% of patients. 42.9% of patients with dominant 70Q/H exhibited EVR versus 88.6% of patients with dominant 70R (P < 0.001). Furthermore, 35.0% of patients with dominant 70Q/H exhibited SVR versus 77.4% with dominant 70R (P < 0.001). However, regardless of the dominant strain, virological response types or the IL28B SNP genotypes, 70Q/H strains always exhibited the same response to treatment as the 70R strains and the percentage of HCV harboring the 70Q/H substitution did not change significantly during treatment. CONCLUSIONS: Although the ratio of 70Q/H to 70R is related to the virological response, 70Q/H strains always exhibited the same response as the 70R strains during PEG-IFNalpha/RBV treatment. Substitution of R70Q/H alone is not enough to lead to resistance to therapy. Positive selection for 70Q/H induced by IFNalpha was not observed.
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Sequence Data
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-
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