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.
journal_name
Virologyjournal_title
Virologyauthors
DesRochers BL,Chen RE,Gounder AP,Pinto AK,Bricker T,Linton CN,Rogers CD,Williams GD,Webby RJ,Boon ACdoi
10.1016/j.virol.2016.04.013subject
Has Abstractpub_date
2016-07-01 00:00:00pages
89-99eissn
0042-6822issn
1096-0341pii
S0042-6822(16)30071-Xjournal_volume
494pub_type
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