Tan, K.S.; Andiappan, A.K.; Lee, B.; Yan, Y.; Liu, J.; Tang, S.A.; Lum, J.; He, T.T.; Ong, Y.K.; Thong, M.; Lim, H.F.; Choi, H.W.; Rotzschke, O.; Chow, V.T.; Wang, D.Y. RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications. Cells 2019, 8, 986.
The human nasal epithelium is the primary site of exposure to influenza virus, the initiator of host responses to influenza and the resultant pathologies. Influenza virus may cause serious respiratory infection resulting in major complications, as well as severe impairment of the airways. Here, we elucidated the global transcriptomic changes during H3N2 infection of human nasal epithelial cells from multiple individuals. Using RNA sequencing, we characterized the differentially-expressed genes and pathways associated with changes occurring at the nasal epithelium following infection. We used in vitro differentiated human nasal epithelial cell culture model derived from seven different donors who had no concurrent history of viral infections. Statistical analysis highlighted strong transcriptomic signatures significantly associated with 24 and 48 h after infection, but not at the earlier 8-h time point. In particular, we found that the influenza infection induced in the nasal epithelium early and altered responses in interferon gamma signaling, B-cell signaling, apoptosis, necrosis, smooth muscle proliferation, and metabolic alterations. These molecular events initiated at the infected nasal epithelium may potentially adversely impact the airway, and thus the genes we identified could serve as potential diagnostic biomarkers or therapeutic targets for influenza infection and associated disease management.
This study was supported by grants awarded to Prof Wang De Yun by the National Medical Research
Council, Singapore (NMRC/CIRG/1458/2016); Dr Yan Yan by the National Natural Science Foundation of China (Grant No.: 81870019); and Dr. Anand Kumar Andiappan by grants from the National Medical Research Council of Singapore (OFYIRG17nov065). Dr Tan Kai Sen is a recipient of fellowship support from the EAACI Research Fellowship 2019; and Dr Anand Kumar Andiappan is a recipient of fellowship support from the EAACI Research Fellowship 2017 and the ERS Short-Term Research Fellowship (STRF). SIgN Immunomonitoring platform is supported by a BMRC IAF 311006 grant and BMRC transition funds #H16/99/b0/011.