Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection

Selinger, M., Wilkie, G. S., Tong, L., Gu, Q., Schnettler, E., Grubhoffer, L. and Kohl, A. (2017) Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection. Journal of General Virology, 98(8), pp. 2043-2060. (doi:10.1099/jgv.0.000853) (PMID:28786780)

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Abstract

Tick-borne encephalitis virus (TBEV) is a member of the genus Flavivirus. It can cause serious infections in humans that may result in encephalitis/meningoencephalitis. Although several studies have described the involvement of specific genes in the host response to TBEV infection in the central nervous system (CNS), the overall network remains poorly characterized. Therefore, we investigated the response of DAOY cells (human medulloblastoma cells derived from cerebellar neurons) to TBEV (Neudoerfl strain, Western subtype) infection to characterize differentially expressed genes by transcriptome analysis. Our results revealed a wide panel of interferon-stimulated genes (ISGs) and pro-inflammatory cytokines, including type III but not type I (or II) interferons (IFNs), which are activated upon TBEV infection, as well as a number of non-coding RNAs, including long non-coding RNAs. To obtain a broader view of the pathways responsible for eliciting an antiviral state in DAOY cells we examined the effect of type I and III IFNs and found that only type I IFN pre-treatment inhibited TBEV production. The cellular response to TBEV showed only partial overlap with gene expression changes induced by IFN-β treatment – suggesting a virus-specific signature – and we identified a group of ISGs that were highly up-regulated following IFN-β treatment. Moreover, a high rate of down-regulation was observed for a wide panel of pro-inflammatory cytokines upon IFN-β treatment. These data can serve as the basis for further studies of host–TBEV interactions and the identification of ISGs and/or lncRNAs with potent antiviral effects in cases of TBEV infection in human neuronal cells.

Item Type:Articles
Additional Information:There is a correction associated with this article at http://eprints.gla.ac.uk/166113/
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Schnettler, Dr Esther and Wilkie, Dr Gavin and Gu, Dr Quan and Tong, Dr Lily and Kohl, Professor Alain and Selinger, Mr Martin
Authors: Selinger, M., Wilkie, G. S., Tong, L., Gu, Q., Schnettler, E., Grubhoffer, L., and Kohl, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of General Virology
Publisher:Society for General Microbiology
ISSN:0022-1317
ISSN (Online):1465-2099
Published Online:08 August 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Journal of General Virology 98(8):2043-2060
Publisher Policy:Reproduced under a Creative Commons License
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