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Basic Characteristics of Mutations
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Mutation Site
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A181T |
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Mutation Site Sentence
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Table 2 |
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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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B;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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Y |
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Treatment
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Adefovir dipivoxil(ADV);Entecavir(ETV) |
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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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32569703
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Title
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Hepatitis B virus mutation pattern rtA181S+T184I+M204I may contribute to multidrug resistance in clinical practice: Analysis of a large cohort of Chinese patients
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Author
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Chen R,Liu Y,Luo D,Si L,Huang B,Wang J,Li X,Cheng F,Xu D,Duan C
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Journal
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Antiviral research
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Journal Info
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2020 Aug;180:104852
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Abstract
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The study aimed to characterize the prevalence and virological features of the rtA181S + T184I + M204I mutant in a large cohort of patients with chronic HBV infection. In total, 22,009 nucleoside/nucleotide analog-treated patients who underwent resistance testing at the Fifth Medical Center of Chinese PLA General Hospital between 2007 and 2016 were enrolled. Serum samples were collected for HBV reverse-transcriptase gene sequencing. Phenotypic analysis of the viral replication capacity and drug susceptibility was performed. The rtA181S mutation was detected in 0.82% (180/22,009) of samples. rtA181S-positive patients had significantly higher lamivudine (LAM), adefovir (ADV), and entecavir (ETV) exposure than rtA181S-negative patients. Of 180 rtA181S-positive patients, 42 had no coexistent resistance mutations, 34 had coexisting LAM-resistance mutation (LAMr), 17 had coexisting ADV-resistance mutation (ADVr), and 86 had coexisting ETV-resistance mutation (ETVr), and one had ADVr + ETVr. rtA181S + T184I + M204I occurred in 79.1% (68/86) of patients with rtA181S + ETVr and 37.8% (68/180) of all rtA181S-positive patients. Longitudinal analysis of the clinical course of resistant mutant evolution for four representative cases showed that rtA181S + T184I + M204I developed in all patients who had received LAM/telbivudine +/- ADV and was receiving ETV or ADV + ETV. Compared with wild-type, the rtA181S + T184I + M204I mutant had 53.7% lower replication capacity and >1000-, 3.9-, and 383.3-fold greater LAM, ADV, and ETV resistance, respectively, but remained sensitive to tenofovir. Artificial elimination of rtA181S from the rtA181S + T184I + M204I mutant restored viral susceptibility to ADV but decreased viral replication capacity. Our study presented the first evidence that HBV rtA181S + T184I + M204I mutation had features of multidrug-resistance that contributed to resistance to both nucleoside and nucleotide analogs.
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Sequence Data
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-
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