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Basic Characteristics of Mutations
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Mutation Site
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V100A |
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Mutation Site Sentence
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Amino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain increase the virulence of H7N7 influenza A 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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PA |
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Standardized Encoding Gene
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PA
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Genotype/Subtype
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H7N7 |
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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
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- |
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Location
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Netherlands |
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Literature Information
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PMID
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27886255
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Title
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Amino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain increase the virulence of H7N7 influenza A virus
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Author
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Hu M,Chu H,Zhang K,Singh K,Li C,Yuan S,Chow BK,Song W,Zhou J,Zheng BJ
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Journal
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Scientific reports
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Journal Info
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2016 Nov 25;6:37800
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Abstract
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The PA N-terminal domain (PA-Nter) is essential for viral transcription and replication. Here we identified PA-Nter substitutions A37S, I61T, V63I and V100A in recently emerged avian influenza A viruses (IAVs) with potential effect on virus pathogenicity and/or host adaptation. We introduced the identified PA-Nter substitutions into avian H7N7 IAV by reverse genetics. Our results showed that single substitution V63I and combined substitutions, I61T/V63I and A37S/I61T/V63I/V100A (Mfour), significantly increased virus growth capacity in mammalian cells. Meanwhile, these substitutions conferred higher virus transcription/replication capacity by producing more mRNA, cRNA and vRNA. Consistently, the polymerase activity and the endonuclease activity were enhanced by these PA-Nter substitutions. Notably, substitutions V63I and Mfour strongly increased virus replication and virulence in mice. Collectively, our findings demonstrated that the PA-Nter substitutions V63I and Mfour enhanced IAV pathogenicity through modification of the polymerase activity and the endonuclease activity, which added to the evolving knowledge of IAV virulence determinants.
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Sequence Data
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-
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