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Basic Characteristics of Mutations
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Mutation Site
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I18V |
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Mutation Site Sentence
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Table 3 |
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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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- |
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Viral Reference
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M62321;NC004102;D90208;D14853;D00944;D10988;D50409;AB031663;D17763;D49374;D63821;Y11604;GU085486;FJ025855;FJ025854;FJ462436;FJ462437;EU392172;EU392170;FJ462432;FJ462438;EU392171;EU392173;FJ839870;FJ462433;FJ462441;FJ462440;FJ462431;FJ462434;FJ462439;FJ839869;Y13184;Y12083;D84262;D84263;D63822;D84265;D84264
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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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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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23095680
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Title
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Naturally occurring mutations to HCV protease inhibitors in treatment-naive patients
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Author
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Paolucci S,Fiorina L,Piralla A,Gulminetti R,Novati S,Barbarini G,Sacchi P,Gatti M,Dossena L,Baldanti F
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Journal
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Virology journal
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Journal Info
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2012 Oct 24;9:245
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Abstract
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BACKGROUND: Protease inhibitors (PIs) to treat hepatitis C (HCV) virus infection have been approved and others are under development. RESULTS: The aims of this study were to illustrate natural polymorphisms in the HCV protease and measure the frequency of PI resistance mutations in different HCV genotypes from PI-naive patients.Direct sequencing of HCV NS3/4A protease was performed in 156 HCV patients naive to PIs who were infected with genotype 1a (n = 31), 1b (n = 39), 2 (n = 30), 3 (n = 33) and 4 (n = 23).Amino acid (aa) substitutions associated with HCV PI resistance were found in 17/156 (10.8%) sequences. Mutations V36L, T54S, V55A/I, and Q80K/L were observed in 29% of patients with genotype 1a, and V55F, Q80L/N and M175L in 10% of patients with genotype 1b. The mutation V158M was found in 3% of patients with genotype 2, D168Q was present in 100% of patients with genotype 3 and D168E was observed in 13% of patients with genotype 4. In addition, multiple aa polymorphisms not associated with PI resistance were detected in patients with genotypes 1a, 1b and 4. CONCLUSIONS: Although major PI resistance mutations were not detected, other resistance mutations conferring low level resistance to PIs together with a number of natural polymorphisms were observed in proteases of PI naive HCV patients. A more extensive analysis is needed to better evaluate the impact of baseline resistance and compensatory mutations in the efficacy of HCV PI treatment.
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Sequence Data
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-
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