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Basic Characteristics of Mutations
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|
Mutation Site
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D413A |
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Mutation Site Sentence
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D413A conferred ganciclovir and cidofovir resistance. |
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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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Pol |
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Standardized Encoding Gene
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UL54
|
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Genotype/Subtype
|
- |
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Viral Reference
|
-
|
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Functional Impact and Mechanisms
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|
Disease
|
Cytomegalovirus infections
|
|
Immune
|
- |
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Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
Y |
|
Treatment
|
ganciclovir;cidofovir |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
17157554
|
|
Title
|
Development of new cytomegalovirus UL97 and DNA polymerase mutations conferring drug resistance after valganciclovir therapy in allogeneic stem cell recipients
|
|
Author
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Marfori JE,Exner MM,Marousek GI,Chou S,Drew WL
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Journal
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Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
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Journal Info
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2007 Feb;38(2):120-5
|
|
Abstract
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BACKGROUND: We report on two allogeneic stem cell transplant recipients who developed cytomegalovirus disease associated with new viral mutations that conferred antiviral drug resistance. METHODS: Blood specimens obtained during symptomatic disease were analyzed for mutations in the CMV UL97 and DNA polymerase genes and new mutations were assessed by recombinant phenotyping. RESULTS: Rising cytomegalovirus (CMV) antigenemia occurred after 4-5 months of preemptive valganciclovir therapy, followed by symptomatic CMV disease including fatal pneumonia in one case. In one case, a new viral UL97 mutation (deletion of codons 601-603) was found which conferred 15-fold increased ganciclovir resistance. In the other case, a known UL97 resistance mutation M460V and a new DNA polymerase (pol) mutation D413A were found. D413A conferred ganciclovir and cidofovir resistance. CONCLUSIONS: Known and newly discovered drug resistance mutations arising during preemptive therapy may complicate post-transplant CMV disease in stem cell recipients. Improved recombinant phenotyping methods enable the rapid quantitation of the resistance conferred by newly identified UL97 and pol mutations.
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Sequence Data
|
-
|