Abstract
We investigated the tropism, host responses, and virulence of two variants of A/Quail/Hong Kong/G1/1997 (H9N2) (H9N2/G1) with D253N and Q591K in the PB2 protein in primary human macrophages and bronchial epithelium in vitro and in mice in vivo. Virus with PB2 D253N and Q591K had greater polymerase activity in minireplicon assays, induced more tumor necrosis factor alpha (TNF-α) in human macrophages, replicated better in differentiated normal human bronchial epithelial (NHBE) cells, and was more pathogenic for mice. Taken together, our studies help define the viral genetic determinants that contribute to pathogenicity of H9N2 viruses.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Substitution
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Amino Acids / genetics
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Animals
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Cells, Cultured
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Disease Models, Animal
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Epithelial Cells / virology
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Humans
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Influenza A Virus, H9N2 Subtype / genetics*
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Influenza A Virus, H9N2 Subtype / pathogenicity*
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Macrophages / virology
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Mice
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Orthomyxoviridae Infections / pathology
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Orthomyxoviridae Infections / virology
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RNA-Dependent RNA Polymerase / genetics*
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RNA-Dependent RNA Polymerase / metabolism*
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Rodent Diseases / pathology
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Rodent Diseases / virology
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Tumor Necrosis Factor-alpha / metabolism
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Viral Proteins / genetics*
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Viral Proteins / metabolism*
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Viral Tropism*
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Virulence Factors / genetics*
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Virulence Factors / metabolism*
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Virus Replication
Substances
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Amino Acids
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PB2 protein, Influenzavirus A
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Tumor Necrosis Factor-alpha
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Viral Proteins
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Virulence Factors
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RNA-Dependent RNA Polymerase