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Effects of the PA-X and PB1-F2 Proteins on the Virulence of the 2009 Pandemic H1N1 Influenza A Virus in Mice

tetano

Editor, Senior Moderator
Front Cell Infect Microbiol. 2019 Sep 3;9:315. doi: 10.3389/fcimb.2019.00315. eCollection 2019.
[h=1]Effects of the PA-X and PB1-F2 Proteins on the Virulence of the 2009 Pandemic H1N1 Influenza A Virus in Mice.[/h] Ma J[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Li S[SUP]4[/SUP], Li K[SUP]4[/SUP], Wang X[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Li S[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h] 1 College of Veterinary Medicine, South China Agricultural University, Guangzhou, China. 2 Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, China. 3 Guangdong Technological Engineering Research Center for Pet, Guangzhou, China. 4 School of Life Science and Engineering, Foshan University, Foshan, China.

[h=3]Abstract[/h] There have been several previous reports showing that PA-X and PB1-F2 proteins can regulate innate immune responses and may play roles in the adaptation of influenza viruses to new hosts. In this research, we investigated, for the first time, the combined effects of PA-X and PB1-F2 proteins on viral virulence in mice. Based on the 2009 pH1N1 A/Guangdong/1057/2010 virus backbone, four viruses encoding different combinations of full-length or truncated PA-X and PB1-F2 proteins were rescued by a reverse genetic engineering system. We analyzed viral replication, host-shutoff activity, in vitro viral pathogenicity and in vivo host immune response. We found that simultaneously expressing the full-length PA-X and PB1-F2 proteins enhanced viral replication in vitro through increasing the accumulation of the RNP complex protein and enhanced viral pathogenicity in mice during the early stage of infection. Furthermore, PA-X and PB1-F2 simultaneously regulated the host innate response, and different forms of PB1-F2 proteins may have impacts on the host shutoff activity induced by the PA-X protein. Our results provide a better understanding of the mechanisms of PA-X and PB1-F2 proteins during viral replication, pathogenicity and host immune response.


[h=4]KEYWORDS:[/h] PA-X; PB1-F2; host-shutoff; influenza; mice

PMID: 31552197 PMCID: PMC6734165 DOI: 10.3389/fcimb.2019.00315
Free PMC Article
 
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