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.

Highlights

  • ‘Downregulation of effectors involved in either transcription (POLR2A) or translation (RNA28S5, RN7SL2, RN7SL3) suggests a possible TBEV-driven transcriptional or translational shut off in host cells

  • ‘3.03’ on page 20 in column ‘IFN-b + TBEV’ was corrected to ‘MARCH3’

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Summary

Introduction

On page 2046, section‚ ‘Host response-associated genes, including type III IFNs, are activated upon TBEV infection of DAOY cells’, the first appearance of ‘RNA28S5’ should be changed to ‘CTD-2328D6.1’ and the final appearance of ‘RNA28S5’ should be removed from the following section of text. ‘RNA28S5, RN7SL2, NOTCH3, COL1A1, BCL9L, BCORL1, POLR2A, FAM71D, IGF2, RN7SL3 and HSPG2 were found to be the most strongly down-regulated genes (fold-change >2.5; Fig. 4 and Table S5).

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