The Unfolded Protein Response is required early during TBEV infection to trigger the interferon response

Flaviviruses are a major cause of disease in humans and animals worldwide. Tick-borne encephalitis virus (TBEV) is the most relevant arthropod-borne flavivirus endemic in Europe and is the etiological agent of tick-borne encephalitis, a potentially fatal infection of the central nervous system. In our recent work we demonstrated that TBEV is able to trigger the stress response of infected cells leading to the formation of stress granules (SG) (Albornoz et al. 2014). We also found that the formation of SG in TBEV infected cells is delayed, following the same delayed kinetic of the IFN response (Miorin et al. 2012). Indeed, while TBEV replication is evident at early time points post infection, SG and IFN-\u3b2 mRNA become detectable only after 16 hours. Transcriptome analysis of TBEV infected cells showed that, in addition to interferon and interferon stimulated genes, also genes of the unfolded protein response (UPR) were activated. Interestingly, the spliced form of XBP1 and phosphorylation of PERK occurred early during infection (