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Basic Characteristics of Mutations
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Mutation Site
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R193Q |
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Mutation Site Sentence
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TABLE 1 |
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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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NS1 |
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Standardized Encoding Gene
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NS
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Genotype/Subtype
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H3N2 |
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Viral Reference
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EPI_ISL_134450
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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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Y |
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Treatment
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- |
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Location
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Canada |
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Literature Information
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PMID
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25246391
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Title
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Multiple influenza A (H3N2) mutations conferring resistance to neuraminidase inhibitors in a bone marrow transplant recipient
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Author
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Eshaghi A,Shalhoub S,Rosenfeld P,Li A,Higgins RR,Stogios PJ,Savchenko A,Bastien N,Li Y,Rotstein C,Gubbay JB
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Journal
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Antimicrobial agents and chemotherapy
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Journal Info
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2014 Dec;58(12):7188-97
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Abstract
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Immunocompromised patients are predisposed to infections caused by influenza virus. Influenza virus may produce considerable morbidity, including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. This approach may promote the emergence of resistant strains. Characterization of neuraminidase (NA) inhibitor (NAI)-resistant strains of influenza A virus is essential for documenting causes of resistance. In this study, using quantitative real-time PCR along with conventional Sanger sequencing, we identified an NAI-resistant strain of influenza A (H3N2) virus in an immunocompromised patient. In-depth analysis by deep gene sequencing revealed that various known markers of antiviral resistance, including transient R292K and Q136K substitutions and a sustained E119K (N2 numbering) substitution in the NA protein emerged during prolonged antiviral therapy. In addition, a combination of a 4-amino-acid deletion at residues 245 to 248 (Delta245-248) accompanied by the E119V substitution occurred, causing resistance to or reduced inhibition by NAIs (oseltamivir, zanamivir, and peramivir). Resistant variants within a pool of viral quasispecies arose during combined antiviral treatment. More research is needed to understand the interplay of drug resistance mutations, viral fitness, and transmission.
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Sequence Data
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KJ734739-KJ734779
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