tetano
Editor, Senior Moderator
J Proteome Res. 2015 Sep 18. [Epub ahead of print]
[h=1]Highly Pathogenic H5N1 and Novel H7N9 Influenza A Viruses Induce more Profound Proteomic Host Responses than Seasonal and Pandemic H1N1 Strains.[/h] Simon PF, McCorrister S, Hu P, Chong P, Silaghi A, Westmacott GR, Coombs KM, Kobasa D.
[h=3]Abstract[/h] 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 1h, 3h and 6h post-infection. Our analyses revealed that both H7N9 and H5N1 strains induced more profound changes to the A549 global proteome compared to 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.
PMID: 26381135 [PubMed - as supplied by publisher]
[h=1]Highly Pathogenic H5N1 and Novel H7N9 Influenza A Viruses Induce more Profound Proteomic Host Responses than Seasonal and Pandemic H1N1 Strains.[/h] Simon PF, McCorrister S, Hu P, Chong P, Silaghi A, Westmacott GR, Coombs KM, Kobasa D.
[h=3]Abstract[/h] 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 1h, 3h and 6h post-infection. Our analyses revealed that both H7N9 and H5N1 strains induced more profound changes to the A549 global proteome compared to 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.
PMID: 26381135 [PubMed - as supplied by publisher]