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Virology. 2016 Apr 19;494:89-99. doi: 10.1016/j.virol.2016.04.013. [Epub ahead of print]
Residues in the PB2 and PA genes contribute to the pathogenicity of avian H7N3 influenza A virus in DBA/2 mice.
DesRochers BL1, Chen RE1, Gounder AP1, Pinto AK1, Bricker T1, Linton CN1, Rogers CD2, Williams GD1, Webby RJ2, Boon AC3.
Author information
Abstract
Replication and transmission of avian influenza virus in humans poses a pandemic threat. The molecular determinants that facilitate this process are not well understood. We used DBA/2 mice to identify viral factors that mediate the difference in pathogenesis between a virulent (H7N3) and a non-virulent (H7N9) avian influenza virus from North America. In vitro and in vivo characterization of reassortant viruses identified the PB2 and PA polymerase genes as major determinants of H7N3 pathogenesis. Analysis of individual residues in the PB2 and PA genes identified position 358 (E358V) in PB2 and positions 190 (P190S) and 400 (Q400P) in PA that reduced the virulence of H7N3 virus. The E358V and P190S substitutions also caused reduced inflammation after infection. Our results suggest that specific residues in the polymerase proteins PB2 and PA are important for replication and virulence of avian influenza viruses in a mammalian host.
Copyright ? 2016 Elsevier Inc. All rights reserved.
KEYWORDS:
Avian influenza virus; DBA/2J; H7 subtype; Pathogenesis
PMID: 27105450 [PubMed - as supplied by publisher]
Residues in the PB2 and PA genes contribute to the pathogenicity of avian H7N3 influenza A virus in DBA/2 mice.
DesRochers BL1, Chen RE1, Gounder AP1, Pinto AK1, Bricker T1, Linton CN1, Rogers CD2, Williams GD1, Webby RJ2, Boon AC3.
Author information
Abstract
Replication and transmission of avian influenza virus in humans poses a pandemic threat. The molecular determinants that facilitate this process are not well understood. We used DBA/2 mice to identify viral factors that mediate the difference in pathogenesis between a virulent (H7N3) and a non-virulent (H7N9) avian influenza virus from North America. In vitro and in vivo characterization of reassortant viruses identified the PB2 and PA polymerase genes as major determinants of H7N3 pathogenesis. Analysis of individual residues in the PB2 and PA genes identified position 358 (E358V) in PB2 and positions 190 (P190S) and 400 (Q400P) in PA that reduced the virulence of H7N3 virus. The E358V and P190S substitutions also caused reduced inflammation after infection. Our results suggest that specific residues in the polymerase proteins PB2 and PA are important for replication and virulence of avian influenza viruses in a mammalian host.
Copyright ? 2016 Elsevier Inc. All rights reserved.
KEYWORDS:
Avian influenza virus; DBA/2J; H7 subtype; Pathogenesis
PMID: 27105450 [PubMed - as supplied by publisher]