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Basic Characteristics of Mutations
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Mutation Site
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L450V |
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Mutation Site Sentence
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By comparison with the consensus sequence of the RT domain among the different viral genotypes (figure 3), only 15 amino acid changes were found to be related to antiviral treatment: the L528M mutation (domain B), detected in 2 of the 4 patients with breakthrough of virus (1 responder and 1 nonresponder) and already described in famciclovir-resistant strains, and 14 novel mutations detected in 7 patients, 3 (N419T, A529V, and V539I) in 2 responders and 11 (T418S, A434P, P440L, H448N, L450I, L450V, L463F, H481Q, V555E, N596T, and V601E) in 5 nonresponders. |
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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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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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Clinical and Epidemiological Correlations
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Clinical Information
|
- |
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Treatment
|
- |
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Location
|
- |
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Literature Information
|
|
PMID
|
10762559
|
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Title
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Evolution of hepatitis B virus polymerase gene sequence during famciclovir therapy for chronic hepatitis B
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Author
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Seigneres B,Pichoud C,Ahmed SS,Hantz O,Trepo C,Zoulim F
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Journal
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The Journal of infectious diseases
|
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Journal Info
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2000 Apr;181(4):1221-33
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Abstract
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Prolonged administration of nucleoside analogues for chronic hepatitis B may result in the emergence of hepatitis B viral polymerase mutants. To gain insight into the mechanism involved in the virus's resistance to famciclovir, the amino acid sequences of the terminal protein and reverse-transcriptase (RT) domains of the viral polymerase were determined during therapy among 28 patients. The antiviral response was independent of viral genotypes, and nonresponse to famciclovir was associated with a complex variability of the RT domain. No mutation in the YMDD motif was observed, whereas an L528M mutation was clearly selected by famciclovir treatment in 2 patients, as well as 14 novel mutations in 7 patients. Clone sequence analysis of the RT domains of patients undergoing retreatment with famciclovir and/or lamivudine showed the selection of a preexisting drug-resistant mutant in one case and indicated that sequential antiviral therapy may allow the rapid selection of resistant strains.
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Sequence Data
|
-
|
|
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