Abstract
We examined the molecular basis of virulence of pandemic H1N1/09 influenza viruses by reverse genetics based on two H1N1/09 virus isolates (A/California/04/2009 [CA04] and A/swine/Shandong/731/2009 [SD731]) with contrasting pathogenicities in mice. We found that four amino acid mutations (P224S in the PA protein [PA-P224S], PB2-T588I, NA-V106I, and NS1-I123V) contributed to the lethal phenotype of SD731. In particular, the PA-P224S mutation when combined with PA-A70V in CA04 drastically reduced the virus's 50% mouse lethal dose (LD50), by almost 1,000-fold.
Publication types
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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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Female
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Humans
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Influenza A Virus, H1N1 Subtype / enzymology*
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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, Human / epidemiology
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Influenza, Human / virology*
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Mice
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Mice, Inbred BALB C
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Molecular Sequence Data
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Mutation*
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North America / epidemiology
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Orthomyxoviridae Infections / veterinary*
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Orthomyxoviridae Infections / virology
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Pandemics
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RNA-Dependent RNA Polymerase / genetics*
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RNA-Dependent RNA Polymerase / metabolism
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Swine
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Swine Diseases / virology*
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Viral Proteins / genetics*
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Viral Proteins / metabolism
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Virulence
Substances
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PA protein, influenza viruses
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Viral Proteins
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RNA-Dependent RNA Polymerase
Associated data
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GENBANK/HQ533864
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GENBANK/HQ533866
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GENBANK/HQ533868
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GENBANK/HQ533871
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GENBANK/HQ533872
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GENBANK/JF951848
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