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Basic Characteristics of Mutations
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Mutation Site
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N597D |
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Mutation Site Sentence
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Successful valganciclovir treatment of post-transplant cytomegalovirus infection in the presence of UL97 mutation N597D. |
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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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UL97 |
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Standardized Encoding Gene
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UL97
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Genotype/Subtype
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- |
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Viral Reference
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T2211
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Functional Impact and Mechanisms
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Disease
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Cytomegalovirus infections
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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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Y |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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19152402
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Title
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Successful valganciclovir treatment of post-transplant cytomegalovirus infection in the presence of UL97 mutation N597D
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Author
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Iwasenko JM,Scott GM,Rawlinson WD,Keogh A,Mitchell D,Chou S
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Journal
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Journal of medical virology
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Journal Info
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2009 Mar;81(3):507-10
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Abstract
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Mutations in the human cytomegalovirus (CMV) UL97 protein kinase are the most common mechanism of ganciclovir (GCV) resistance in the clinical setting. A CMV strain with a previously unrecognized UL97 mutation N597D was identified in the blood of a heart transplant recipient who experienced a persistent CMV infection with high viral loads accompanying pain and fever while receiving valganciclovir (valGCV) therapy. The N597D mutation was transferred by mutagenesis to an antiviral sensitive CMV strain for analysis of antiviral susceptibility by standardized phenotypic assay. Recombinant phenotyping showed N597D conferred a less than twofold increase in GCV IC(50) compared to the sensitive control strain. Despite the presence of this mutation, valGCV eventually resolved the infection after 6 weeks of therapy. A subsequent CMV reactivation was also responsive to valganciclovir. This case illustrates the diversity of UL97 mutations in the codon segment 590-607 usually associated with GCV resistance, with some mutations producing minimal levels of resistance that do not preclude a therapeutic response to the drug. Accurate interpretation of genotypic test results ultimately requires experimental determination of the level of resistance conferred by newly discovered UL97 mutations.
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Sequence Data
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-
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