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Basic Characteristics of Mutations
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Mutation Site
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V173L |
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Mutation Site Sentence
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The principal substitutions outside the YMDD motif were rtV173L and rtL180M (located outside the C domain), which have been reported to partially restore the in vitro replication capacity of variants with substitutions in the YMDD motif |
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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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- |
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Viral Reference
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AM073272-AM073968
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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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- |
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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) |
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Location
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- |
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Literature Information
|
|
PMID
|
16378967
|
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Title
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Dynamics of hepatitis B virus resistance to lamivudine
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Author
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Pallier C,Castera L,Soulier A,Hezode C,Nordmann P,Dhumeaux D,Pawlotsky JM
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Journal
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Journal of virology
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Journal Info
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2006 Jan;80(2):643-53
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Abstract
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Lamivudine was the first approved inhibitor of hepatitis B virus (HBV) reverse transcriptase (RT). Lamivudine resistance develops in 53% to 76% of patients after 3 years of treatment. We extensively characterized the dynamics of HBV quasispecies variant populations in four HBV-infected patients who developed lamivudine resistance. Virological breakthrough was preceded by 2 to 4 months by the emergence of quasispecies variants bearing amino acid substitutions at RT position 204, i.e., within the YMDD catalytic motif (rtM204V/I). Three patients had a gradual switch from a YMDD variant population at baseline to a 100% lamivudine-resistant variant population, whereas the remaining patient had a fluctuating pattern of resistance variant dynamics. Careful analysis of amino acid substitutions located outside domain C of HBV RT, including those known to partially restore replication capacities in vitro, showed that the in vivo replication of HBV variants is driven by multiple forces, including intrinsic replicative advantages conferred by mutations accumulating outside domain C and the changing environment in which these variants replicate. Our findings also suggest that individual treatment optimization will require sensitive methods capable of detecting the emergence of viral resistance before the relevant variants acquire optimal replicative capacities.
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Sequence Data
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-
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