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Basic Characteristics of Mutations
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Mutation Site
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A181G |
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Mutation Site Sentence
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The addition of the rtA181G change to this triple mutant resulted in a 1.5-fold replication impairment, whereas the addition of rtI169L and rtV173L+P177S increased by 1.3- and 1.8-fold, respectively, the replication capacity of the same triple mutant. |
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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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- |
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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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Entecavir(ETV) |
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Location
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- |
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Literature Information
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PMID
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17239478
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Title
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Stepwise process for the development of entecavir resistance in a chronic hepatitis B virus infected patient
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Author
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Villet S,Ollivet A,Pichoud C,Barraud L,Villeneuve JP,Trepo C,Zoulim F
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Journal
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Journal of hepatology
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Journal Info
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2007 Mar;46(3):531-8
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Abstract
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BACKGROUND/AIMS: Complex mutants may be selected under sequential anti-VHB pressures. We analyzed the genotypic and phenotypic evolution of the viral quasi-species of a patient who developed resistance to entecavir following lamivudine breakthrough. METHODS: The polymerase gene was amplified, cloned and sequenced at different time points. Hepatoma cell lines were transfected to compare the replication capacity of HBV mutants and their drug susceptibility. RESULTS: A mixture of lamivudine-resistant HBV strains coexisted following viral breakthrough to lamivudine, all harboring the rtM204V mutation. The rtV173L+L180M+M204V dominant mutant displayed strong lamivudine-resistance and the highest replication capacity. Following the switch to entecavir, the viral load dropped but the lamivudine-resistant strains continued to be selected. Three years later, the viral load rose again, and a complex mixture of entecavir-resistant strains, all harboring the lamivudine-resistance signature rtL180M+M204V and the rtS202G mutation were observed. Although the rtL180M+S202G+M204V variant, that prevailed at the end of entecavir therapy, did not show the highest viral genome replication capacity, it conferred one of the strongest resistance levels to entecavir. CONCLUSIONS: We report the selection of complex HBV mutants that escaped lamivudine and entecavir antiviral pressures. Genotypic and phenotypic analysis provided additional information to understand the process of HBV variant selection.
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Sequence Data
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-
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