Giuseppe
Emeritus
PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells. (J Virol., abstract, edited)
5. J Virol. 2010 Feb 24. [Epub ahead of print]
PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells.
Bussey KA, Bousse TL, Desmet EA, Kim B, Takimoto T. - Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY.
The direct infection of humans with highly pathogenic avian H5N1 influenza viruses has suggested viral mutation as one mechanism for the emergence of novel human influenza A viruses. Although the polymerase complex is known to be a key component in host adaptation, mutations that enhance the polymerase activity of avian viruses in mammalian hosts are not fully characterized. Genomic comparison of influenza A virus isolates has identified highly conserved residues in influenza proteins that are specific to either human or avian viruses, including ten residues in PB2. We characterized the activity of avian polymerase complexes containing avian-to-human mutations at these conserved PB2 residues, and found that, in addition to the E627K mutation, the PB2 mutation T271A enhances polymerase activity in human cells. We confirmed the effects of the T271A mutation using recombinant WSN viruses containing avian NP and polymerase genes with wild-type (WT) or mutant PB2. The 271A virus showed enhanced growth over WT in mammalian cells in vitro. The 271A mutant did not increase viral pathogenicity significantly in mice compared to the 627K mutant, but enhanced the lung virus titer. Also, cell infiltration was evident in lungs of 271A infected mice compared to WT. Interestingly, the avian-derived PB2 of the 2009 pandemic H1N1 influenza virus has 271A. Characterization of the polymerase activity of A/California/04/2009 (H1N1) and corresponding PB2 mutants indicates that the high polymerase activity of the pandemic strain in mammalian cells is, in part, dependent on 271A. Our results clearly indicate the contribution of PB2 amino acid 271 to enhanced polymerase activity and viral growth in mammalian hosts.
PMID: 20181719 [PubMed - as supplied by publisher]
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5. J Virol. 2010 Feb 24. [Epub ahead of print]
PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells.
Bussey KA, Bousse TL, Desmet EA, Kim B, Takimoto T. - Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY.
The direct infection of humans with highly pathogenic avian H5N1 influenza viruses has suggested viral mutation as one mechanism for the emergence of novel human influenza A viruses. Although the polymerase complex is known to be a key component in host adaptation, mutations that enhance the polymerase activity of avian viruses in mammalian hosts are not fully characterized. Genomic comparison of influenza A virus isolates has identified highly conserved residues in influenza proteins that are specific to either human or avian viruses, including ten residues in PB2. We characterized the activity of avian polymerase complexes containing avian-to-human mutations at these conserved PB2 residues, and found that, in addition to the E627K mutation, the PB2 mutation T271A enhances polymerase activity in human cells. We confirmed the effects of the T271A mutation using recombinant WSN viruses containing avian NP and polymerase genes with wild-type (WT) or mutant PB2. The 271A virus showed enhanced growth over WT in mammalian cells in vitro. The 271A mutant did not increase viral pathogenicity significantly in mice compared to the 627K mutant, but enhanced the lung virus titer. Also, cell infiltration was evident in lungs of 271A infected mice compared to WT. Interestingly, the avian-derived PB2 of the 2009 pandemic H1N1 influenza virus has 271A. Characterization of the polymerase activity of A/California/04/2009 (H1N1) and corresponding PB2 mutants indicates that the high polymerase activity of the pandemic strain in mammalian cells is, in part, dependent on 271A. Our results clearly indicate the contribution of PB2 amino acid 271 to enhanced polymerase activity and viral growth in mammalian hosts.
PMID: 20181719 [PubMed - as supplied by publisher]
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