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Basic Characteristics of Mutations
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Mutation Site
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Y100S |
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Mutation Site Sentence
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By co-variation analysis, correlations were observed for R122P+S167L (phi=0.68, P=0.01), T116N+S143L (phi=0.53, P=0.03), and Y100S+S143L (phi=0.67, p<0.001). |
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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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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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D |
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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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Occult HBV 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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22086128
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Title
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Novel HBsAg markers tightly correlate with occult HBV infection and strongly affect HBsAg detection
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Author
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Svicher V,Cento V,Bernassola M,Neumann-Fraune M,Van Hemert F,Chen M,Salpini R,Liu C,Longo R,Visca M,Romano S,Micheli V,Bertoli A,Gori C,Ceccherini-Silberstein F,Sarrecchia C,Andreoni M,Angelico M,Ursitti A,Spano A,Zhang JM,Verheyen J,Cappiello G,Perno CF
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Journal
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Antiviral research
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Journal Info
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2012 Jan;93(1):86-93
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Abstract
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Occult HBV infection (OBI) is a threat for the safety of blood-supply, and has been associated with the onset of HBV-related hepatocellular carcinoma and lymphomagenesis. Nevertheless, genetic markers in HBsAg (particularly in D-genotype, the most common in Europe) significantly associated with OBI in vivo are missing. Thus, the goal of this study is to define: (i) prevalence and clinical profile of OBI among blood-donors; (ii) HBsAg-mutations associated with OBI; (iii) their impact on HBsAg-detection. OBI was searched among 422,278 blood-donors screened by Nucleic-Acid-Testing. Following Taormina-OBI-definition, 26 (0.006%) OBI-patients were identified. Despite viremia <50IU/ml, HBsAg-sequences were obtained for 25/26 patients (24/25 genotype-D). OBI-associated mutations were identified by comparing OBI-HBsAg with that of 82 chronically-infected (genotype-D) patients as control. Twenty HBsAg-mutations significantly correlated for the first time with OBI. By structural analysis, they localized in the major HBV B-cell-epitope, and in HBsAg-capsid interaction region. 14/24 OBI-patients (58.8%) carried in median 3 such mutations (IQR:2.0-6.0) against 0 in chronically-infected patients. By co-variation analysis, correlations were observed for R122P+S167L (phi=0.68, P=0.01), T116N+S143L (phi=0.53, P=0.03), and Y100S+S143L (phi=0.67, p<0.001). Mutants (obtained by site-directed mutagenesis) carrying T116N, T116N+S143L, R122P, R122P+Q101R, or R122P+S167L strongly decreased HBsAg-reactivity (54.9+/-22.6S/CO, 31.2+/-12.0S/CO, 6.1+/-2.4S/CO, 3.0+/-1.0S/CO and 3.9+/-1.3S/CO, respectively) compared to wild-type (306.8+/-64.1S/CO). Even more, Y100S and Y100S+S143L supernatants show no detectable-HBsAg (experiments in quadruplicate). In conclusions, unique HBsAg-mutations in genotype-D, different than those described in genotypes B/C (rarely found in western countries), tightly correlate with OBI, and strongly affect HBsAg-detection. By altering HBV-antigenicity and/or viral-particle maturation, they may affect full-reliability of universal diagnostic-assays for HBsAg-detection.
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Sequence Data
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-
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