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Basic Characteristics of Mutations
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Mutation Site
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L595S |
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Mutation Site Sentence
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Arbitrarily, three groups of mutants could be defined: (i) pUL97 carrying the mutations M460V and H520Q exhibited a very low mean residual GCV phosphorylation (<10%); (ii) pUL97 carrying M460I, A594V, L595S, L595del showed a mean residual GCV phosphorylation between 10 and 20%; and (iii) pUL97 with C592G, L595F, G598S, C607Y mutations exhibited a mean GCV phosphorylation in the range of 30–50%. |
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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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-
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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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- |
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Treatment
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GCV |
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Location
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Italy |
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Literature Information
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PMID
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11888658
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Title
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Mutations in the UL97 ORF of ganciclovir-resistant clinical cytomegalovirus isolates differentially affect GCV phosphorylation as determined in a recombinant vaccinia virus system
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Author
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Baldanti F,Michel D,Simoncini L,Heuschmid M,Zimmermann A,Minisini R,Schaarschmidt P,Schmid T,Gerna G,Mertens T
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Journal
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Antiviral research
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Journal Info
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2002 Apr;54(1):59-67
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Abstract
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Mutations in the human cytomegalovirus (HCMV) UL97 phosphotransferase have been associated with ganciclovir (GCV) resistance due to an impairment of GCV monophosphorylation. Vaccinia virus recombinants (rVV) were generated that encoded different HCMV UL97 proteins (pUL97) with mutations previously detected in resistant HCMV clinical isolates at codons 460, 520, 592, 594, 595, 598 and 607. These rVVs allowed quantification of GCV phosphorylation catalyzed by the different mutated pUL97s. When compared to rVV-UL97 wild type, mean levels of residual intracellular GCV phosphorylation differed by a factor of 10 for the mutated UL97 proteins ranging from 5.2 to 51.8%. Mutations M460V (located in a UL97 region homologous to domain VIb of protein kinases) and H520Q (located in a cytomegalovirus-specific, functionally critical domain) were responsible for the lowest levels of residual GCV phosphorylation (9.3 and 5.2%). Mutations in a region homologous to the domain IX had a lower impact on GCV phosphorylation (15.8-51.8%). The relevance of pUL97 mutation G598S in inducing GCV resistance was demonstrated for the first time.
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Sequence Data
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-
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