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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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Besides the sites for the primary (rtM204V/I) and secondary (rtL180M) lamivudine-resistance mutations identified in five patients, only one additional site with significant changes in intra-host populations was shared by HBV in three patients and four sites by HBV in two patients. |
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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
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Hepatitis B Virus Infection
|
|
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
|
JQ707299-JQ707774
|