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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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Instead, in the NS5A gene, the R30Q, L31M and/or Y93H were detected by both sequencing analyses in seven patients (Table 2). |
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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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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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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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Italy |
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Literature Information
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PMID
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31269695
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Title
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NS5A Gene Analysis by Next Generation Sequencing in HCV Nosocomial Transmission Clusters of HCV Genotype 1b Infected Patients
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Author
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Bellocchi MC,Aragri M,Carioti L,Fabeni L,Pipitone RM,Brancaccio G,Sorbo MC,Barbaliscia S,Di Maio VC,Bronte F,Grimaudo S,Mazzucco W,Frigeri F,Cantone M,Pinto A,Perno CF,Craxi A,Gaeta GB,Di Marco V,Ceccherini-Silberstein F
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Journal
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Cells
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Journal Info
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2019 Jul 2;8(7):666
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Abstract
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Background: The aim of the study was to investigate the intra-host variability through next-generation-sequencing (NGS) of the NS5A-gene in nosocomial transmission-clusters observed in two Italian hospitals among hepatitis C virus (HCV)-genotype-1b infected patients. Methods: HCV-sequencing was performed by Sanger-sequencing (NS3 + NS5A + NS5B) and by NGS (NS5A, MiSeq-Illumina) in 15 HCV-1b infected patients [five acute with onco-hematologic-disease and 10 (4/6 acute/chronic) with beta-thalassemia]. Resistance-associated-substitutions (RAS) were analysed by Geno2pheno-algorithm. Nucleotide-sequence-variability (NSV, at 1%, 2%, 5%, 10% and 15% NGS-cutoffs) and Shannon entropy were estimated. Phylogenetic analysis was performed by Mega6-software and Bayesian-analysis. Results: Phylogenetic analysis showed five transmission-clusters: one involving four HCV-acute onco-hematologic-patients; one involving three HCV-chronic beta-thalassemia-patients and three involving both HCV-acute and chronic beta-thalassemia-patients. The NS5A-RAS Y93H was found in seven patients, distributed differently among chronic/acute patients involved in the same transmission-clusters, independently from the host-genetic IL-28-polymorphism. The intra-host NSV was higher in chronic-patients versus acute-patients, at all cutoffs analyzed (p < 0.05). Even though Shannon-entropy was higher in chronic-patients, significantly higher values were observed only in chronic beta-thalassemia-patients versus acute beta-thalassemia-patients (p = 0.01). Conclusions: In nosocomial HCV transmission-clusters, the intra-host HCV quasispecies divergence in patients with acute-infection was very low in comparison to that in chronic-infection. The NS5A-RAS Y93H was often transmitted and distributed differently within the same transmission-clusters, independently from the IL-28-polymorphism.
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Sequence Data
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-
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