Abstract
The nonstructural protein NS1 of influenza A virus blocks the development of host antiviral responses by inhibiting polyadenylation of cellular pre-mRNA. NS1 also promotes the synthesis of viral proteins by stimulating mRNA translation. Here, we show that recombinant NS1 proteins of human pandemic H1N1/2009, avian highly pathogenic H5N1, and low pathogenic H5N2 influenza strains differentially affected these two cellular processes: NS1 of the two avian strains, in contrast to NS1 of H1N1/2009, stimulated translation of reporter mRNA in cell-free translation system; NS1 of H5N1 was an effective inhibitor of cellular pre-mRNA polyadenylation in A549 cells, unlike NS1 of H5N2 and H1N1/2009. We identified key amino acids in NS1 that contribute to its activity in these two basic cellular processes. Thus, we identified strain-specific differences between influenza virus NS1 proteins in pre-mRNA polyadenylation and mRNA translation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Humans
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Influenza A Virus, H1N1 Subtype / genetics
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Influenza A Virus, H1N1 Subtype / pathogenicity
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Influenza A Virus, H5N1 Subtype / genetics
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Influenza A Virus, H5N1 Subtype / pathogenicity
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Influenza A Virus, H5N2 Subtype / genetics
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Influenza A Virus, H5N2 Subtype / pathogenicity
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Influenza A virus / genetics*
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Influenza A virus / pathogenicity
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Models, Chemical
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Molecular Sequence Data
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Orthomyxoviridae Infections / epidemiology
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Orthomyxoviridae Infections / physiopathology
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Orthomyxoviridae Infections / virology*
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Pandemics
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Polyadenylation / physiology
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Protein Biosynthesis / physiology*
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Protein Stability
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Protein Structure, Tertiary
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RNA Precursors / metabolism
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Species Specificity
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Viral Nonstructural Proteins / chemistry
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Viral Nonstructural Proteins / genetics*
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Viral Nonstructural Proteins / metabolism*
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Virulence
Substances
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INS1 protein, influenza virus
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RNA Precursors
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Viral Nonstructural Proteins