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Front Microbiol. 2018 Nov 14;9:2685. doi: 10.3389/fmicb.2018.02685. eCollection 2018.

Comparative Transcriptomic and Metagenomic Analyses of Influenza Virus-Infected Nasal Epithelial Cells From Multiple Individuals Reveal Specific Nasal-Initiated Signatures.

Author information

1
Department of Otolaryngology, National University of Singapore, Singapore, Singapore.
2
Center for Interventional Medicine, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
3
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
4
Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
5
Institute of Molecular and Cell Biology, A∗STAR, Singapore, Singapore.
6
Department of Physiology, National University of Singapore, Singapore, Singapore.
7
School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
8
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Abstract

In vitro and in vivo research based on cell lines and animals are likely to be insufficient in elucidating authentic biological and physiological phenomena mimicking human systems, especially for generating pre-clinical data on targets and biomarkers. There is an obvious need for a model that can further bridge the gap in translating pre-clinical findings into clinical applications. We have previously generated a model of in vitro differentiated human nasal epithelial cells (hNECs) which elucidated the nasal-initiated repertoire of immune responses against respiratory viruses such as influenza A virus and rhinovirus. To assess their clinical utility, we performed a microarray analysis of influenza virus-infected hNECs to elucidate nasal epithelial-initiated responses. This was followed by a metagenomic analysis which revealed transcriptomic changes comparable with clinical influenza datasets. The primary target of influenza infection was observed to be the initiator of innate and adaptive immune genes, leaning toward type-1 inflammatory activation. In addition, the model also elucidated a down-regulation of metabolic processes specific to the nasal epithelium, and not present in other models. Furthermore, the hNEC model detected all 11 gene signatures unique to influenza infection identified from a previous study, thus supporting the utility of nasal-based diagnosis in clinical settings. In conclusion, this study highlights that hNECs can serve as a model for nasal-based clinical translational studies and diagnosis to unravel nasal epithelial responses to influenza in the population, and as a means to identify novel molecular diagnostic markers of severity.

KEYWORDS:

human nasal epithelial cells; influenza; meta-analysis; pre-clinical model; transcriptomics

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