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Mutations in the H7 HA and PB1 genes of avian influenza a viruses increase viral pathogenicity and contact transmission in guinea pigs

tetano

Editor, Senior Moderator
Emerg Microbes Infect. 2019;8(1):1324-1336. doi: 10.1080/22221751.2019.1663131.
[h=1]Mutations in the H7 HA and PB1 genes of avian influenza a viruses increase viral pathogenicity and contact transmission in guinea pigs.[/h] Dreier C[SUP]1,[/SUP][SUP]2[/SUP], Resa-Infante P[SUP]3,[/SUP][SUP]4[/SUP], Thiele S[SUP]1[/SUP], Stanelle-Bertram S[SUP]1[/SUP], Walendy-Gnir? K[SUP]1[/SUP], Speiseder T[SUP]1[/SUP], Preuss A[SUP]1[/SUP], M?ller Z[SUP]1[/SUP], Klenk HD[SUP]5[/SUP], Stech J[SUP]6[/SUP], Gabriel G[SUP]1,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h] 1 Viral Zoonosis -One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology , Hamburg , Germany. 2 Current address: University of Ulm , Ulm , Germany . 3 Institute of Virology, University of Veterinary Medicine , Hannover , Germany. 4 Current address: IrsiCaixa AIDS Research Institute , Barcelona , Spain . 5 Institute for Virology, Philipps University of Marburg , Marburg , Germany. 6 Institute for Molecular Virology and Cell Biology, Friedrich-Loeffler-Institute , Greifswald , Germany.

[h=3]Abstract[/h] Avian influenza A viruses (AIV) of the H7 subtype continue to evolve posing a pandemic threat. However, molecular markers of H7N7 AIV pathogenicity and transmission in mammals remain poorly understood. In this study, we performed a systematic in vitro and in vivo analysis by comparing an H7N7 highly pathogenic AIV and its ferret adapted variant. Passaging an H7N7 AIV in ferrets led to six mutations in genes encoding the viral polymerase complex and the viral surface proteins. Here, we show that mutations in the H7 hemagglutinin gene cause increased pathogenicity in mice. Contact transmission between guinea pigs required additional mutations in the gene encoding the polymerase subunit PB1. Thus, particular vigilance is required with respect to HA and PB1 mutations as predictive molecular markers to assess the pandemic risk posed by emerging H7 avian influenza viruses.


[h=4]KEYWORDS:[/h] H7 avian influenza A viruses; HA and PB1 gene mutations; guinea pigs; pathogenicity; transmission

PMID: 31503518 DOI: 10.1080/22221751.2019.1663131
 
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