tetano
Editor, Senior Moderator
Virol J. 2016 Mar 15;13(1):42. doi: 10.1186/s12985-016-0498-2.
[h=1]Human H7N9 virus induces a more pronounced pro-inflammatory cytokine but an attenuated interferon response in human bronchial epithelial cells when compared with an epidemiologically-linked chicken H7N9 virus.[/h] To KK[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Lau CC[SUP]1[/SUP], Woo PC[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Lau SK[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Chan JF[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Chan KH[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Zhang AJ[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Chen H[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Yuen KY[SUP]6,[/SUP][SUP]7,[/SUP][SUP]8,[/SUP][SUP]9,[/SUP][SUP]10[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Avian influenza virus H7N9 has jumped species barrier, causing sporadic human infections since 2013. We have previously isolated an H7N9 virus from a patient, and an H7N9 virus from a chicken in a live poultry market where the patient visited during the incubation period. These two viruses were genetically highly similar. This study sought to use a human bronchial epithelial cell line model to infer the virulence of these H7N9 viruses in humans.
[h=4]METHODS:[/h] Human bronchial epithelial cell line Calu-3 was infected with two H7N9 viruses (human H7N9-HU and chicken H7N9-CK), a human H5N1 virus and a human 2009 pandemic H1N1 virus. The infected cell lysate was collected at different time points post-infection for the determination of the levels of pro-inflammatory cytokines (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]), anti-inflammatory cytokines (interleukin 10 [IL-10] and transforming growth factor beta [TGF-β]), chemokines (interleukin 8 [IL-8] and monocyte chemoattractant protein 1 [MCP-1]), and interferons (interferon β [IFN-β] and interferon lambda 1 [IFNL1]). The viral load in the cell lysate was also measured.
[h=4]RESULTS:[/h] Comparison of the human and chicken H7N9 viruses showed that H7N9-HU induced significantly higher levels of TNF-α at 12 h post-infection, and significantly higher levels of IL-8 from 12 to 48 h post-infection than those of H7N9-CK. However, the level of IFNL1 was lower for H7N9-HU than that of H7N9-CK at 48 h post-infection (P < 0.001). H7N9-HU had significantly higher viral loads than H7N9-CK at 3 and 6 h post-infection. H5N1 induced significantly higher levels of TNF-α, IL-6, IL-8, IL-10 and MCP-1 than those of H7N9 viruses at 48 h post-infection. Conversely, H1N1 induced lower levels of TNF-α, IL-10, MCP-1, IFNL1 and IFN-β when compared with H7N9 viruses at the same time point.
[h=4]CONCLUSIONS:[/h] H7N9-HU induced higher levels of pro-inflammatory IL-6 and IL-8 and exhibited a more rapid viral replication than H7N9-CK. However, the level of antiviral IFNL1 was lower for H7N9-HU than H7N9-CK. Our results suggest that the gained properties in modulating human innate immunity by H7N9-HU transformed it to be a more virulent virus in humans than H7N9-CK.
[h=4]KEYWORDS:[/h] Avian influenza virus; Chemokine; Chicken; Cytokine; H7N9; Human; IL-8; Interferon; Interferon lambda 1; Viral load
PMID: 26975414 [PubMed - in process] PMCID: PMC4791762 Free PMC Article
[h=1]Human H7N9 virus induces a more pronounced pro-inflammatory cytokine but an attenuated interferon response in human bronchial epithelial cells when compared with an epidemiologically-linked chicken H7N9 virus.[/h] To KK[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Lau CC[SUP]1[/SUP], Woo PC[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Lau SK[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Chan JF[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Chan KH[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Zhang AJ[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Chen H[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP], Yuen KY[SUP]6,[/SUP][SUP]7,[/SUP][SUP]8,[/SUP][SUP]9,[/SUP][SUP]10[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Avian influenza virus H7N9 has jumped species barrier, causing sporadic human infections since 2013. We have previously isolated an H7N9 virus from a patient, and an H7N9 virus from a chicken in a live poultry market where the patient visited during the incubation period. These two viruses were genetically highly similar. This study sought to use a human bronchial epithelial cell line model to infer the virulence of these H7N9 viruses in humans.
[h=4]METHODS:[/h] Human bronchial epithelial cell line Calu-3 was infected with two H7N9 viruses (human H7N9-HU and chicken H7N9-CK), a human H5N1 virus and a human 2009 pandemic H1N1 virus. The infected cell lysate was collected at different time points post-infection for the determination of the levels of pro-inflammatory cytokines (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]), anti-inflammatory cytokines (interleukin 10 [IL-10] and transforming growth factor beta [TGF-β]), chemokines (interleukin 8 [IL-8] and monocyte chemoattractant protein 1 [MCP-1]), and interferons (interferon β [IFN-β] and interferon lambda 1 [IFNL1]). The viral load in the cell lysate was also measured.
[h=4]RESULTS:[/h] Comparison of the human and chicken H7N9 viruses showed that H7N9-HU induced significantly higher levels of TNF-α at 12 h post-infection, and significantly higher levels of IL-8 from 12 to 48 h post-infection than those of H7N9-CK. However, the level of IFNL1 was lower for H7N9-HU than that of H7N9-CK at 48 h post-infection (P < 0.001). H7N9-HU had significantly higher viral loads than H7N9-CK at 3 and 6 h post-infection. H5N1 induced significantly higher levels of TNF-α, IL-6, IL-8, IL-10 and MCP-1 than those of H7N9 viruses at 48 h post-infection. Conversely, H1N1 induced lower levels of TNF-α, IL-10, MCP-1, IFNL1 and IFN-β when compared with H7N9 viruses at the same time point.
[h=4]CONCLUSIONS:[/h] H7N9-HU induced higher levels of pro-inflammatory IL-6 and IL-8 and exhibited a more rapid viral replication than H7N9-CK. However, the level of antiviral IFNL1 was lower for H7N9-HU than H7N9-CK. Our results suggest that the gained properties in modulating human innate immunity by H7N9-HU transformed it to be a more virulent virus in humans than H7N9-CK.
[h=4]KEYWORDS:[/h] Avian influenza virus; Chemokine; Chicken; Cytokine; H7N9; Human; IL-8; Interferon; Interferon lambda 1; Viral load
PMID: 26975414 [PubMed - in process] PMCID: PMC4791762 Free PMC Article