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

0479247 - BC 2018 RIV GB eng J - Journal Article
Selinger, Martin - Wilkie, G. S. - Tong, L. - Gu, Q. - Schnettler, E. - Grubhoffer, Libor - Kohl, A.
Analysis of tick-borne encephalitis virus-induced host responses in human cells of neuronal origin and interferon-mediated protection.
Journal of General Virology. Roč. 98, č. 8 (2017), s. 2043-2060. ISSN 0022-1317. E-ISSN 1465-2099
R&D Projects: GA ČR GA15-03044S
Institutional support: RVO:60077344
Keywords : blood-brain-barrier * long noncoding RNAs * double-stranded-RNA * interferon * immune-response * gene-expression * stimulated genes * human astrocytes * viral-infection * protein * tick-borne encephalitis virus * neuronal cells * transcriptome analysis * host response * interferon
OECD category: Virology
Impact factor: 2.514, year: 2017

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 pretreatment inhibited TBEV production. The cellular response to TBEV showed only partial overlap with gene expression changes induced by IFN-beta treatment suggesting a virus-specific signature and we identified a group of ISGs that were highly up-regulated following IFN-beta treatment. Moreover, a high rate of down-regulation was observed for a wide panel of pro-inflammatory cytokines upon IFN-beta 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.
Permanent Link: http://hdl.handle.net/11104/0275238