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Basic Characteristics of Mutations
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Mutation Site
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L180C |
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Mutation Site Sentence
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The mutant had a rtL180C/M204I genotype and was detected after 2 years of therapy with lamivudine. |
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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
|
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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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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Clinical and Epidemiological Correlations
|
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Clinical Information
|
- |
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Treatment
|
Lamivudine(LAM) |
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Location
|
- |
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Literature Information
|
|
PMID
|
15980328
|
|
Title
|
Emergence of a novel mutation in the FLLA region of hepatitis B virus during lamivudine therapy
|
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Author
|
Pai SB,Bozdayi AM,Pai RB,Beker T,Sarioglu M,Turkyilmaz AR,Grier J,Yurdaydin C,Schinazi RF
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Journal
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Antimicrobial agents and chemotherapy
|
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Journal Info
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2005 Jul;49(7):2618-24
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Abstract
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The emergence of resistance to lamivudine has been one of the major stumbling blocks to successful treatment and control of hepatitis B virus (HBV) infections. The major mechanism of resistance has been attributed to the alteration in the YMDD motif of the HBV polymerase due to an amino acid change of rtM204 to V/I and an accompanying rtL180M conversion. A novel mutation pattern in a patient having clinical breakthrough under lamivudine therapy was discovered. The mutant had a rtL180C/M204I genotype and was detected after 2 years of therapy with lamivudine. To characterize this novel variant, site-directed mutagenesis was performed using a vector construct containing the HBV genome. Transient transfection studies in human hepatoma cells with HBV carrying the new mutant demonstrated that the rtL180C/M204I mutant was resistant to lamivudine up to 10 microM. The resistance profile was comparable to that of the previously reported rtL180 M/M204I-containing virus. These observations were further confirmed by generation of stable cultures transfected with the mutant virus.
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Sequence Data
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-
|