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Basic Characteristics of Mutations
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Mutation Site
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G16D |
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Mutation Site Sentence
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Insertion of the ""human-like"" G16-->D mutation into avian NP, which resulted in susceptibility to caspase cleavage, did not rescue virulence, but made the reassortant virus even more attenuated. |
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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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NP |
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Standardized Encoding Gene
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NP
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Genotype/Subtype
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H5N1 |
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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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Vietnam |
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Literature Information
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PMID
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18058063
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Title
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The role of the N-terminal caspase cleavage site in the nucleoprotein of influenza A virus in vitro and in vivo
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Author
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Lipatov AS,Yen HL,Salomon R,Ozaki H,Hoffmann E,Webster RG
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Journal
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Archives of virology
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Journal Info
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2008;153(3):427-34
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Abstract
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The N-terminal caspase cleavage in the nucleoprotein (NP) of influenza A virus is correlated with the host origin of the virus, thus could be a molecular determinant for host range. We studied how mutations targeting the NP cleavage motif of human and avian influenza viruses affect virus replication in vitro and in vivo. The ""avian-like"" D16-->G substitution in the NP, which makes this protein resistant to cleavage, did not significantly affect the human A/Puerto Rico/8/34 (H1N1) virus replication in vitro but decreased the lethality of this virus in mice by 68-fold. Gene incompatibility contributed to the attenuated phenotype of the reassortant A/Puerto Rico/8/34 virus with avian NP derived from A/Teal/Hong Kong/w312/97 (H6N1) virus in vitro and in vivo. Insertion of the ""human-like"" G16-->D mutation into avian NP, which resulted in susceptibility to caspase cleavage, did not rescue virulence, but made the reassortant virus even more attenuated. Introducing the human-like G16-->D substitution into the NP of highly pathogenic A/Vietnam/1203/04 (H5N1) virus decreased lethality in mice. We confirmed that position 16, which associated with the N-terminal caspase cleavage of the NP, is important for optimal virus fitness in vitro and in vivo. An avian-like mutation at position 16 in the NP of human virus as well as a human-like substitution at this residue in avian NP both resulted in virus attenuation.
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Sequence Data
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-
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