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Basic Characteristics of Mutations
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Mutation Site
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E21K |
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Mutation Site Sentence
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As predicted, the HA1-E21K change in Cal/09 lowered the threshold pH for fusion from 5.4 to 5.0, which can be explained by the introduction of the stabilizing salt bridge between HA1-K21 and HA2-E47. |
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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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HA1 |
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Standardized Encoding Gene
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HA
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Genotype/Subtype
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H1N1 |
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Viral Reference
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A/California/7/2009 wild type;A/Brisbane/10/2010 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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- |
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Location
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- |
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Literature Information
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PMID
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24391498
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Title
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A single amino acid in the stalk region of the H1N1pdm influenza virus HA protein affects viral fusion, stability and infectivity
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Author
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Cotter CR,Jin H,Chen Z
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Journal
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PLoS pathogens
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Journal Info
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2014 Jan;10(1):e1003831
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Abstract
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The 2009 H1N1 pandemic (H1N1pdm) viruses have evolved to contain an E47K substitution in the HA2 subunit of the stalk region of the hemagglutinin (HA) protein. The biological significance of this single amino acid change was investigated by comparing A/California/7/2009 (HA2-E47) with a later strain, A/Brisbane/10/2010 (HA2-K47). The E47K change was found to reduce the threshold pH for membrane fusion from 5.4 to 5.0. An inter-monomer salt bridge between K47 in HA2 and E21 in HA1, a neighboring highly conserved residue, which stabilized the trimer structure, was found to be responsible for the reduced threshold pH for fusion. The higher structural and acid stability of the HA trimer caused by the E47K change also conferred higher viral thermal stability and infectivity in ferrets, suggesting a fitness advantage for the E47K evolutionary change in humans. Our study indicated that the pH of HA fusion activation is an important factor for influenza virus replication and host adaptation. The identification of this genetic signature in the HA stalk region that influences vaccine virus thermal stability also has significant implications for influenza vaccine production.
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Sequence Data
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-
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