PMID- 26381135 OWN - NLM STAT- MEDLINE DCOM- 20160912 LR - 20220317 IS - 1535-3907 (Electronic) IS - 1535-3893 (Linking) VI - 14 IP - 11 DP - 2015 Nov 6 TI - Highly Pathogenic H5N1 and Novel H7N9 Influenza A Viruses Induce More Profound Proteomic Host Responses than Seasonal and Pandemic H1N1 Strains. PG - 4511-23 LID - 10.1021/acs.jproteome.5b00196 [doi] AB - Influenza A viruses (IAV) are important human and animal pathogens with potential for causing pandemics. IAVs exhibit a wide spectrum of clinical illness in humans, from relatively mild infections by seasonal strains to acute respiratory distress syndrome during infections with some highly pathogenic avian influenza (HPAI) viruses. In the present study, we infected A549 human cells with seasonal H1N1 (sH1N1), 2009 pandemic H1N1 (pdmH1N1), or novel H7N9 and HPAI H5N1 strains. We used multiplexed isobaric tags for relative and absolute quantification to measure proteomic host responses to these different strains at 1, 3, and 6 h post-infection. Our analyses revealed that both H7N9 and H5N1 strains induced more profound changes to the A549 global proteome compared to those with low-pathogenicity H1N1 virus infection, which correlates with the higher pathogenicity these strains exhibit at the organismal level. Bioinformatics analysis revealed important modulation of the nuclear factor erythroid 2-related factor 2 (NRF2) oxidative stress response in infection. Cellular fractionation and Western blotting suggested that the phosphorylated form of NRF2 is not imported to the nucleus in H5N1 and H7N9 virus infections. Fibronectin was also strongly inhibited in infection with H5N1 and H7N9 strains. This is the first known comparative proteomic study of the host response to H7N9, H5N1, and H1N1 viruses and the first time NRF2 is shown to be implicated in infection with highly pathogenic strains of influenza. FAU - Simon, Philippe Francois AU - Simon PF AD - Department of Medical Microbiology and Infectious Diseases, University of Manitoba , Winnipeg, Manitoba, R3E 0J9 Canada. FAU - McCorrister, Stuart AU - McCorrister S FAU - Hu, Pingzhao AU - Hu P AD - Department of Biochemistry and Medical Genetics, University of Manitoba , Winnipeg, Manitoba, R3T 2N2 Canada. FAU - Chong, Patrick AU - Chong P FAU - Silaghi, Alex AU - Silaghi A AD - Department of Medical Microbiology and Infectious Diseases, University of Manitoba , Winnipeg, Manitoba, R3E 0J9 Canada. FAU - Westmacott, Garrett AU - Westmacott G FAU - Coombs, Kevin M AU - Coombs KM AD - Department of Medical Microbiology and Infectious Diseases, University of Manitoba , Winnipeg, Manitoba, R3E 0J9 Canada. AD - Manitoba Center for Proteomics and Systems Biology, University of Manitoba , Winnipeg, Manitoba, R3E 3P4 Canada. FAU - Kobasa, Darwyn AU - Kobasa D AD - Department of Medical Microbiology and Infectious Diseases, University of Manitoba , Winnipeg, Manitoba, R3E 0J9 Canada. LA - eng GR - MOP-106713/Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151009 PL - United States TA - J Proteome Res JT - Journal of proteome research JID - 101128775 RN - 0 (Fibronectins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NFE2L2 protein, human) RN - 0 (Proteome) SB - IM MH - Cell Line, Tumor MH - Cell Nucleus/metabolism/virology MH - Computational Biology/methods MH - Cytosol/metabolism/virology MH - Epithelial Cells/*metabolism/virology MH - Fibronectins/*genetics/metabolism MH - Gene Expression Regulation MH - Host-Pathogen Interactions MH - Humans MH - Influenza A Virus, H1N1 Subtype/*physiology MH - Influenza A Virus, H5N1 Subtype/*pathogenicity/physiology MH - Influenza A Virus, H7N9 Subtype/*pathogenicity/physiology MH - NF-E2-Related Factor 2/*genetics/metabolism MH - Oxidative Stress MH - Phosphorylation MH - Protein Transport MH - Proteome/*genetics/metabolism MH - Respiratory Mucosa/metabolism/virology MH - Signal Transduction MH - Virulence OTO - NOTNLM OT - FN1 OT - H1N1 OT - H5N1 OT - H7N9 OT - NRF2 OT - avian influenza OT - fibronectin OT - oxidative stress EDAT- 2015/09/19 06:00 MHDA- 2016/09/13 06:00 CRDT- 2015/09/19 06:00 PHST- 2015/09/19 06:00 [entrez] PHST- 2015/09/19 06:00 [pubmed] PHST- 2016/09/13 06:00 [medline] AID - 10.1021/acs.jproteome.5b00196 [doi] PST - ppublish SO - J Proteome Res. 2015 Nov 6;14(11):4511-23. doi: 10.1021/acs.jproteome.5b00196. Epub 2015 Oct 9.