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Basic Characteristics of Mutations
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Mutation Site
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E119V |
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Mutation Site Sentence
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RESULTS: The E119G and E119V mutations conferred a multidrug resistance phenotype to many NAIs but severely compromised viral fitness. |
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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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-
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Functional Impact and Mechanisms
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Disease
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Influenza A
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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
|
zanamivir;peramivir;A-315675 |
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Location
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- |
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Literature Information
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PMID
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21148493
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Title
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Generation and characterization of recombinant pandemic influenza A(H1N1) viruses resistant to neuraminidase inhibitors
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Author
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Pizzorno A,Bouhy X,Abed Y,Boivin G
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Journal
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The Journal of infectious diseases
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Journal Info
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2011 Jan 1;203(1):25-31
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Abstract
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BACKGROUND: Neuraminidase inhibitors (NAIs) play a key role in the management of influenza epidemics and pandemics. Given the novel pandemic influenza A(H1N1) (pH1N1) virus and the restricted number of approved anti-influenza drugs, evaluation of potential drug-resistant variants is of high priority. METHODS: Recombinant pH1N1 viruses were generated by reverse genetics, expressing either the wild-type or any of 9 mutant neuraminidase (NA) proteins (N2 numbering: E119G, E119V, D198G, I222V, H274Y, N294S, S334N, I222V-H274Y, and H274Y-S334N). We evaluated these recombinant viruses for their resistance phenotype to 4 NAIs (oseltamivir, zanamivir, peramivir, and A-315675), NA enzymatic activity, and replicative capacity. RESULTS: The E119G and E119V mutations conferred a multidrug resistance phenotype to many NAIs but severely compromised viral fitness. The oseltamivir- and peramivir-resistance phenotype was confirmed for the H274Y and N294S mutants, although both viruses remained susceptible to zanamivir. Remarkably, the I222V mutation had a synergistic effect on the oseltamivir- and peramivir-resistance phenotype of H274Y and compensated for reduced viral fitness, raising concerns about the potential emergence and dissemination of this double-mutant virus. CONCLUSIONS: This study highlights the importance of continuous monitoring of antiviral drug resistance in clinical samples as well as the need to develop new agents and combination strategies.
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Sequence Data
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-
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