Abstract
Triple reassortant swine influenza viruses (SIVs) and 2009 pandemic H1N1 (pH1N1) virus contain an avian-origin PB2 with 271A, 590S, 591R, and 627E. To evaluate the role of PB2 271A, 590S, and 591R in the replication and virulence of SIV, single (1930-TX98-PB2-271T)-, double (1930-TX98-PB2-590A591A)-, and triple (1930-TX98-PB2-271T590A591A)-mutated viruses were generated in the background of the H1N1 A/swine/Iowa/15/30 (1930) virus with an avian-origin PB2 from the triple-reassortant A/swine/Texas/4199-2/98 (TX98) virus, called the parental 1930-TX98-PB2. Compared to parental virus and single- and double-mutated viruses, the triple-mutated virus replicated less efficiently in cell cultures and was attenuated in mice. These results suggest that a combination of 271A with the 590/591 SR polymorphism is critical for pH1N1 and triple-reassortant SIVs for efficient replication and adaptation in mammals.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Line
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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, H1N1 Subtype / physiology
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Influenza, Human / virology
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Mice
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Mutation
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Orthomyxoviridae Infections / veterinary*
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Orthomyxoviridae Infections / virology
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Polymorphism, Single Nucleotide*
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RNA-Dependent RNA Polymerase / chemistry*
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RNA-Dependent RNA Polymerase / genetics*
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RNA-Dependent RNA Polymerase / metabolism
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Reassortant Viruses / genetics
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Reassortant Viruses / pathogenicity
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Reassortant Viruses / physiology
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Swine
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Swine Diseases / mortality
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Swine Diseases / virology*
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Viral Proteins / chemistry*
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Viral Proteins / genetics*
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Viral Proteins / metabolism
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Virulence
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Virus Replication*
Substances
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PB2 protein, Influenzavirus A
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Viral Proteins
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RNA-Dependent RNA Polymerase