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Basic Characteristics of Mutations
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Mutation Site
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A1814C |
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Mutation Site Sentence
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Six (24%) of the study sequences had preC start codon mutations: three (3321, T033, and N60) had A1814C, two (3354 and 3658) had A1814T, and one (3269) had G1816T. |
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Mutation Level
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Nucleotide level |
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Mutation Type
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Gene/Protein/Region
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PreC |
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Standardized Encoding Gene
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C
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Genotype/Subtype
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- |
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Viral Reference
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X02763;AF297622
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Functional Impact and Mechanisms
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Disease
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HBV-HIV Coinfection
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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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South Africa |
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Literature Information
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PMID
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23925707
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Title
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Variability of the preC/C region of hepatitis B virus genotype A from a South African cohort predominantly infected with HIV
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Author
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Mayaphi SH,Martin DJ,Mphahlele MJ,Blackard JT,Bowyer SM
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Journal
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Journal of medical virology
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Journal Info
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2013 Nov;85(11):1883-92
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Abstract
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Hepatitis B virus (HBV) is a serious global health problem, and HBV genotype is an important determinant of disease progression and treatment outcome. The aim of this study was to assess variations of the precore/core (preC/C) region in HBV genotype A. Sequencing of the preC/C and surface (S) genes of HBV was performed on plasma samples from 20 HBV/HIV co-infected and 5 HBV mono-infected individuals. All preC/C study sequences clustered with subgenotype A1, except for two which clustered with subgenotype D4 reference strains. The nucleotide and amino acid variability was far higher in the preC/C region than in the S region. Mutations associated with reduction or failure of HBV e-antigen (HBeAg) production were observed, with a preC start codon mutation being common (24%). Other mutations (e.g., P5H/L and I97L) associated with severe liver disease were also noticed, some of which were located in the major histocompatibility restricted sites. PreC/C intergenotype nucleotide divergence was >7%, while subgenotypes differed by 2.5-7%. Several study sequences were highly divergent from other African subgenotype A1 strains. This study showed that HBeAg-negative chronic hepatitis B is underestimated in subgenotype A1, and also highlighted the variant South African A1 strains. The major advantage of preC/C sequencing is that it informs patient management as HBeAg-negative chronic hepatitis B responds poorly to conventional interferon-alpha therapy, and some guidelines treat HBeAg-negative chronic hepatitis B differently from HBeAg-positive chronic hepatitis B. These data suggest that subgenotype A1 may be more involved in severe HBV-related diseases.
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Sequence Data
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-
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