Abstract
BackgroundAvian 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.MethodsHuman 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.ResultsComparison 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.ConclusionsH7N9-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.
Highlights
Avian influenza virus H7N9 has jumped species barrier, causing sporadic human infections since 2013
The level of antiviral interferon lambda 1 (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
Summary
Avian influenza virus H7N9 has jumped species barrier, causing sporadic human infections since 2013. Unlike most patients with seasonal or pandemic influenza virus infection which present with self-limiting acute upper respiratory illness, the majority of patients with laboratory-confirmed H7N9 infections present with rapidly progressive community-acquired pneumonia, leukopenia, lymphopenia, thrombocytopenia, impaired coagulation profile, deranged liver and renal function, and some patients succumbed with adult respiratory distress syndrome and multiorgan dysfunction [12,13,14,15]. These differences in clinical severity and pathology among H7N9, H5N1 and H1N1 may be related to the differential ability of the viruses to induce cytokine and chemokine response. The suboptimal humoral response induced by H7N9 virus may be related to their internal genes [20]
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