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Article

RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications

by
Kai Sen Tan
1,†,
Anand Kumar Andiappan
2,†,
Bernett Lee
2,‡,
Yan Yan
1,3,‡,
Jing Liu
1,‡,
See Aik Tang
2,
Josephine Lum
2, 1,
Yew Kwang Ong
1,
Mark Thong
1,
Hui Fang Lim
4,5,
Hyung Won Choi
5,6,
Olaf Rotzschke
2,
Vincent T Chow
7,* and
De Yun Wang
1,*
1
Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
2
Singapore Immunology Network (SIgN), A*STAR, Singapore 138648, Singapore
3
Center for Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
4
Division of Respiratory and Critical Care Medicine, National University Hospital, Singapore 119074, Singapore
5
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
6
Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Singapore
7
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
Cells 2019, 8(9), 986; https://doi.org/10.3390/cells8090986
Received: 5 July 2019 / Revised: 15 August 2019 / Accepted: 23 August 2019 / Published: 27 August 2019
(This article belongs to the Special Issue Host–Pathogen Interactions During Influenza Virus Infection)
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Abstract

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. View Full-Text
Keywords: influenza; H3N2 virus; human nasal epithelial cells (hNECs); RNA sequencing; transcriptomics; epithelial responses; pathogenesis influenza; H3N2 virus; human nasal epithelial cells (hNECs); RNA sequencing; transcriptomics; epithelial responses; pathogenesis
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MDPI and ACS Style

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. https://doi.org/10.3390/cells8090986

AMA Style

Tan KS, Andiappan AK, Lee B, Yan Y, Liu J, Tang SA, Lum J, He TT, Ong YK, Thong M, Lim HF, Choi HW, Rotzschke O, Chow VT, Wang DY. 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(9):986. https://doi.org/10.3390/cells8090986

Chicago/Turabian Style

Tan, Kai S., Anand K. Andiappan, Bernett Lee, Yan Yan, Jing Liu, See A. Tang, Josephine Lum, Ting T. He, Yew K. Ong, Mark Thong, Hui F. Lim, Hyung W. Choi, Olaf Rotzschke, Vincent T. Chow, and De Y. Wang. 2019. "RNA Sequencing of H3N2 Influenza Virus-Infected Human Nasal Epithelial Cells from Multiple Subjects Reveals Molecular Pathways Associated with Tissue Injury and Complications" Cells 8, no. 9: 986. https://doi.org/10.3390/cells8090986

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