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

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Comparative Transcriptomic and Metagenomic Analyses of Influenza Virus-Infected Nasal Epithelial Cells From Multiple Individuals Reveal Specific Nasal-Initiated Signatures
Title:
Comparative Transcriptomic and Metagenomic Analyses of Influenza Virus-Infected Nasal Epithelial Cells From Multiple Individuals Reveal Specific Nasal-Initiated Signatures
Journal Title:
Frontiers in Microbiology
Keywords:
Publication Date:
14 November 2018
Citation:
Tan KS, Yan Y, Koh WLH, Li L, Choi H, Tran T, Sugrue R, Wang DY and Chow VT (2018) Comparative Transcriptomic and Metagenomic Analyses of Influenza Virus-Infected Nasal Epithelial Cells From Multiple Individuals Reveal Specific Nasal-Initiated Signatures. Front. Microbiol. 9:2685. doi: 10.3389/fmicb.2018.02685
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.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This study was supported by grants from the National Medical Research Council, Singapore (NMRC/CIRG/1362/2013, NMRC/CIRG/1458/2016 and NMRC/CG/M009). Part of this work was presented at the Nature Conference on Viral Infection and Immune Response, Wuhan, China, October 21–24, 2016; European Academy of Allergy and Clinical Immunology Conference, Helsinki, Finland, June 17–21, 2017; and International Union of Microbiological Societies Congress, Singapore, July 17–21, 2017
Description:
ISSN:
1664-302X
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