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Basic Characteristics of Mutations
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Mutation Site
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P1S |
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Mutation Site Sentence
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Ariants in each population differed from each other by the same substitution at the same position, rtP1S, and between populations by four substitutions at the same positions, with two of these substitutions being rtM204V and rtL180M. |
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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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G;D;B;C;A |
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Viral Reference
|
-
|
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Functional Impact and Mechanisms
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Disease
|
Hepatitis B Virus Infection
|
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Immune
|
- |
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Target Gene
|
-
|
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Clinical and Epidemiological Correlations
|
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Clinical Information
|
Y |
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Treatment
|
- |
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Location
|
- |
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Literature Information
|
|
PMID
|
22510694
|
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Title
|
Convergence and coevolution of hepatitis B virus drug resistance
|
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Author
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Thai H,Campo DS,Lara J,Dimitrova Z,Ramachandran S,Xia G,Ganova-Raeva L,Teo CG,Lok A,Khudyakov Y
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Journal
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Nature communications
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Journal Info
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2012 Apr 17;3:789
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Abstract
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Treatment with lamivudine of patients infected with hepatitis B virus (HBV) results in a high rate of drug resistance, which is primarily associated with the rtM204I/V substitution in the HBV reverse transcriptase domain. Here we show that the rtM204I/V substitution, although essential, is insufficient for establishing resistance against lamivudine. The analysis of 639 HBV whole-genome sequences obtained from 11 patients shows that rtM204I/V is independently acquired by more than one intra-host HBV variant, indicating the convergent nature of lamivudine resistance. The differential capacity of HBV variants to develop drug resistance suggests that fitness effects of drug-resistance mutations depend on the genetic structure of the HBV genome. An analysis of Bayesian networks that connect rtM204I/V to many sites of HBV proteins confirms that lamivudine resistance is a complex trait encoded by the entire HBV genome rather than by a single mutation. These findings have implications for public health and offer a more general framework for understanding drug resistance.
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Sequence Data
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JQ707299-JQ707774
|