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Basic Characteristics of Mutations
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Mutation Site
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N295S |
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Mutation Site Sentence
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The N295S mutation in the wild-type virus (Chungbuk-Y275-N295S) was associated with a reduction in oseltamivir resistance (0.2-fold decrease in IC50 compared with that of the wild-type virus), whereas N295S mutation of the mutant virus containing histidine (H) at NA residue 275 (Chungbuk-Y275H-N295S) was associated with an increase in oseltamivir resistance (40.3-fold increase in IC50 compared with that of Chungbuk-Y275H mutant virus). |
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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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NA |
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Standardized Encoding Gene
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NA
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Genotype/Subtype
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H1N1 |
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Viral Reference
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A/Chungbuk/4448/2008 wild type
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Functional Impact and Mechanisms
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Disease
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Cell line
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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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oseltamivir |
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Location
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South Korea |
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Literature Information
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PMID
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24524021
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Title
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Generation and Characterization of Recombinant Influenza A(H1N1) Viruses Resistant to Neuraminidase Inhibitors
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Author
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Choi W,Shin JY,Jeong HE,Jeong MJ,Kim SJ,Lee JY,Kang C
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Journal
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Osong public health and research perspectives
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Journal Info
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2013 Dec;4(6):323-8
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Abstract
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OBJECTIVES: To examine the effect of neuraminidase (NA) mutations on the NA inhibitor (NAI) resistance phenotype, the recombinant influenza A/Chungbuk/4448/2008(H1N1) virus isolated in South Korea during the 2008-2009 season was generated by reverse genetics. METHODS: Site-directed mutagenesis was introduced on the NA gene of A/Chungbuk/4448/2008(H1N1) virus, and a total of 23 single, double, and triple mutants were generated. Resistance phenotype of these recombinant viruses was determined by NA-inhibition (NAI) assays based on a fluorometric method using two NAIs (oseltamivir and zanamivir). RESULTS: NA-inhibition assays showed that all the single and double mutants containing the Y275 except the single Y275-E119V mutant conferred important levels of resistance to oseltamivir, whereas all the single, double, and triple mutants containing the E119V mutation were associated with the resistance to zanamivir. CONCLUSION: Considering the effect of mutations in NA gene on the resistance to NAIs, it is important to monitor the possible emergence and dissemination of multidrug-resistant variants in the human population due to amino acid changes at NA gene as well as to develop novel NAIs.
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Sequence Data
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-
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