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Basic Characteristics of Mutations
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Mutation Site
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L180M |
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Mutation Site Sentence
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RESULTS: TDF susceptibilities of lamivudine-resistant clones (rtL180M/M204V) and lamivudine plus entecavir-resistant clones (rtL180M/S202G/M204V) were similar to wild type clones in vitro. |
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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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A;C |
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Viral Reference
|
-
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Functional Impact and Mechanisms
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Disease
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Hepatitis B Virus Infection
|
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Immune
|
- |
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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
|
Lamivudine(LAM);Abacavir(ADV);Tenofovir(TDF) |
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Location
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- |
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Literature Information
|
|
PMID
|
26515673
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Title
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Effect of tenofovir disoproxil fumarate on drug-resistant HBV clones
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Author
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Murakami E,Tsuge M,Hiraga N,Kan H,Uchida T,Masaki K,Nakahara T,Ono A,Miki D,Kawaoka T,Abe H,Imamura M,Aikata H,Ochi H,Hayes CN,Akita T,Tanaka J,Chayama K
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Journal
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The Journal of infection
|
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Journal Info
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2016 Jan;72(1):91-102
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Abstract
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BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) has been approved for chronic hepatitis B treatment, and favorable susceptibility of hepatitis B virus (HBV) has been indicated. However, differences in TDF susceptibility among HBV genotypes and drug-resistant strains are unclear. In this study, TDF susceptibilities between genotypes A and C were evaluated in vitro and in vivo using several drug-resistant HBV clones. METHODS: HBV expression plasmids were constructed from sera of HBV carriers, and drug-resistant substitutions were introduced by site-directed mutagenesis. TDF susceptibility was evaluated by changes of core-associated HBV replication intermediates in vitro or by change of serum HBV DNA in human hepatocyte chimeric mice carrying each HBV clone in vivo. RESULTS: TDF susceptibilities of lamivudine-resistant clones (rtL180M/M204V) and lamivudine plus entecavir-resistant clones (rtL180M/S202G/M204V) were similar to wild type clones in vitro. However, lamivudine plus adefovir-resistant clones (rtA181T/N236T) acquired tolerance to TDF, and the rtN236T mutation was considered to be a causal substitution for TDF resistance. Furthermore, genotypic differences in TDF susceptibility were also observed between genotypes A and C in vitro, and the differences could be confirmed in vivo (p = 0.023). CONCLUSIONS: The present study indicates that TDF susceptibility varies among HBV genotypes and drug-resistant HBV clones.
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Sequence Data
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-
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