Dataset Information

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

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.

SUBMITTER: Tan KS

PROVIDER: S-EPMC6246735 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Tan Kai Sen KS Yan Yan Y Koh Wai Ling Hiromi WLH Li Liang L Choi Hyungwon H Tran Thai T Sugrue Richard R Wang De Yun Y Chow Vincent T VT

Frontiers in microbiology 20181114

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 ...[more]

PMID: 30487780

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Project description:Tacaribe virus (TCRV) is a mammalian arenavirus that was first isolated from artibeus bats in the 1950s. Subsequent experimental infection of Jamaican fruit bats (Artibeus jamaicensis) caused a disease similar to that of naturally infected bats. Although substantial attention has focused on bats as reservoir hosts of viruses that cause human disease, little is known about the interactions between bats and their pathogens. We performed a transcriptome-wide study to illuminate the response of Jamaican fruit bats experimentally infected with TCRV. Differential gene expression analysis of multiple tissues revealed global and organ-specific responses associated with innate antiviral responses, including interferon alpha/beta and Toll-like receptor signaling, activation of complement cascades, and cytokine signaling, among others. Genes encoding proteins involved in adaptive immune responses, such as gamma interferon signaling and costimulation of T cells by the CD28 family, were also altered in response to TCRV infection. Immunoglobulin gene expression was also elevated in the spleens of infected bats, including IgG, IgA, and IgE isotypes. These results indicate an active innate and adaptive immune response to TCRV infection occurred but did not prevent fatal disease. This de novo assembly provides a high-throughput data set of the Jamaican fruit bat and its host response to TCRV infection, which remains a valuable tool to understand the molecular signatures involved in antiviral responses in bats. IMPORTANCE As reservoir hosts of viruses associated with human disease, little is known about the interactions between bats and viruses. Using Jamaican fruit bats infected with Tacaribe virus (TCRV) as a model, we characterized the gene expression responses to infection in different tissues and identified pathways involved with the response to infection. This report is the most detailed gene discovery work in the species to date and the first to describe immune gene expression responses in bats during a pathogenic viral infection.

Dataset Information

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

Publications

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

Similar Datasets

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