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Basic Characteristics of Mutations
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Mutation Site
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E627K |
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Mutation Site Sentence
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We compared H1N1pdm viruses that expressed wild type PB2 (rNY1682-WT), PB2-E627K (rNY1682-E627K), PB2-D701N (rNY1682-D701N), or a PB2-E158G (rNY1682-E158G) substitution that we previously showed significantly increases the pathogenicity of the H1N1pdm 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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PB2 |
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Standardized Encoding Gene
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PB2
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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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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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- |
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Location
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- |
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Literature Information
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PMID
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23799150
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Title
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Asparagine substitution at PB2 residue 701 enhances the replication, pathogenicity, and transmission of the 2009 pandemic H1N1 influenza A virus
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Author
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Zhou B,Pearce MB,Li Y,Wang J,Mason RJ,Tumpey TM,Wentworth DE
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Journal
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PloS one
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Journal Info
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2013 Jun 14;8(6):e67616
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Abstract
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The 2009/2010 pandemic influenza virus (H1N1pdm) contains an avian-lineage PB2 gene that lacks E627K and D701N substitutions important in the pathogenesis and transmission of avian-origin viruses in humans or other mammals. Previous studies have shown that PB2-627K is not necessary because of a compensatory Q591R substitution. The role that PB2-701N plays in the H1N1pdm phenotype is not well understood. Therefore, PB2-D701N was introduced into an H1N1pdm virus (A/New York/1682/2009 (NY1682)) and analyzed in vitro and in vivo. Mini-genome replication assay, in vitro replication characteristics in cell lines, and analysis in the mouse and ferret models demonstrated that PB2-D701N increased virus replication rates and resulted in more severe pathogenicity in mice and more efficient transmission in ferrets. In addition, compared to the NY1682-WT virus, the NY1682-D701N mutant virus induced less IFN-lambda and replicated to a higher titer in primary human alveolar epithelial cells. These findings suggest that the acquisition of the PB2-701N substitution by H1N1pdm viruses may result in more severe disease or increase transmission in humans.
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Sequence Data
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-
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