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Basic Characteristics of Mutations
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Mutation Site
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I38T |
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Mutation Site Sentence
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Rapid detection of an I38T amino acid substitution in influenza polymerase acidic subunit associated with reduced susceptibility to baloxavir marboxil. |
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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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PA |
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Standardized Encoding Gene
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PA
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Genotype/Subtype
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H1N1;H3N2 |
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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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Influenza A
Influenza B
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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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- |
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Location
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baloxavir marboxil |
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Literature Information
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PMID
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32064779
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Title
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Rapid detection of an I38T amino acid substitution in influenza polymerase acidic subunit associated with reduced susceptibility to baloxavir marboxil
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Author
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Nakauchi M,Takashita E,Fujisaki S,Shirakura M,Ogawa R,Morita H,Miura H,Saito S,Watanabe S,Odagiri T,Kageyama T
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Journal
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Influenza and other respiratory viruses
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Journal Info
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2020 Jul;14(4):436-443
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Abstract
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BACKGROUND: The novel cap-dependent endonuclease inhibitor baloxavir marboxil was approved in February 2018 for the treatment of influenza virus infection in Japan. In vitro studies have revealed that an I38T substitution in the polymerase acidic subunit (PA) is associated with reduced susceptibility of influenza viruses to baloxavir. OBJECTIVES: Development of a rapid and simple method for monitoring influenza A(H1N1)pdm09, A(H3N2), and B viruses possessing the I38T substitution in PA. METHODS: Three assays were developed based on RNase H2-dependent PCR (rhPCR) and named A/H1pdm PA_I38T rhPCR, A/H3 PA_I38T rhPCR, and B PA_I38T rhPCR. The assays were evaluated using cDNAs synthesized from in vitro-transcribed PA gene RNA controls, RNAs purified from viruses isolated in the 2017/2018 and 2018/2019 influenza seasons, and RNAs purified from clinical specimens collected in the 2018/2019 influenza season. RESULTS: The assays developed in this study accurately discriminated PA I38 and PA T38 with high sensitivity. CONCLUSIONS: Our assays should be considered a powerful tool for monitoring the emergence of baloxavir-resistant influenza viruses.
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Sequence Data
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-
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