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Basic Characteristics of Mutations
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Mutation Site
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L80V |
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Mutation Site Sentence
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Further analysis shown in Fig. 2Dindicated that rtH55R;rtL80I/V;rtV173L/M;rtL180M and rtL229F/M/V/W preferred to be coexisting with rtM204I/V substitution compared to the rtM204 group |
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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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RT |
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Standardized Encoding Gene
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P
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Genotype/Subtype
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C |
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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 B, 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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- |
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Treatment
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- |
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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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28440785
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Title
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Impacts of HBV rtH55R polymerase substitution on viral replication and rtM204I/V resistance to nucleoside/nucleotide antiviral drugs
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Author
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Xiang KH,Zhao CY,Wang S,Li Y,Su MZ,Wang QY,Xu XZ,Deng J,Zhuang H,Li T
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Journal
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Antiviral therapy
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Journal Info
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2018;23(1):33-42
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Abstract
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BACKGROUND: High genetic variability at the reverse transcriptase (RT) region of HBV could confer resistance to nucleoside/nucleotide analogues (NUCs). The aim of this study was to identify new RT amino acid (AA) substitutions related to NUC resistance. METHODS: HBV RT sequences of genotype C from 501 chronic hepatitis B (CHB) patients were analysed to identify potential RT substitutions related to NUC resistance. In vitro studies without and with NUCs were performed in a HepG2 cell line transfected by clones with RT harbouring wild-type or substituted AA(s) of interest. RESULTS: Among 261 NUC-treated CHB patients, we found a high detection rate of rtM204I/V substitution (30.7% [80/261]). We identified a new substitution of rtH55R, and its detection rate had a significantly increasing trend from 3.8% (9/240) in the untreated group to 7.2% (13/181) or 33.8% (27/80) in the treated group with rtM204 or with rtM204I/V substitutions (P<0.0001). In vitro studies showed that rtH55R had a similar HBV DNA level compared to wild type. The rtH55R+rtM204I clone had a significantly better replication capacity than the rtM204I clone without NUCs (P<0.05). The replication capacity of the rtM204I clone was found to significantly decrease under lamivudine treatment, but this was not found in the rtH55R+rtM204I clone. CONCLUSIONS: We identified a new HBV RT substitution of rtH55R in genotype-C-infected CHB patients. It is frequently found in combination with rtM204I/V substitution under NUC treatment. In vitro studies suggest that it might play some replication compensatory role in rtM204I mutants under lamivudine treatment.
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Sequence Data
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-
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