Viruses, Vol. 13, Pages 2164: IRE1-Mediated Unfolded Protein Response Promotes the Replication of Tick-Borne Flaviviruses in a Virus and Cell-Type Dependent Manner

Viruses, Vol. 13, Pages 2164: IRE1-Mediated Unfolded Protein Response Promotes the Replication of Tick-Borne Flaviviruses in a Virus and Cell-Type Dependent Manner Viruses doi: 10.3390/v13112164 Authors: Veronika J. M. Breitkopf Gerhard Dobler Peter Claus Hassan Y. Naim Imke Steffen Tick-borne flaviviruses (TBFV) can cause severe neurological complications in humans, but differences in tissue tropism and pathogenicity have been described for individual virus strains. Viral protein synthesis leads to the induction of the unfolded protein response (UPR) within infected cells. The IRE1 pathway has been hypothesized to support flavivirus replication by increasing protein and lipid biogenesis. Here, we investigated the role of the UPR in TBFV infection in human astrocytes, neuronal and intestinal cell lines that had been infected with tick-borne encephalitis virus (TBEV) strains Neudoerfl and MucAr-HB-171/11 as well as Langat virus (LGTV). Both TBEV strains replicated better than LGTV in central nervous system (CNS) cells. TBEV strain MucAr-HB-171/11, which is associated with gastrointestinal symptoms, replicated best in intestinal cells. All three viruses activated the inositol-requiring enzyme 1 (IRE1) pathway via the X-box binding protein 1 (XBP1). Interestingly, the neurotropic TBEV strain Neudoerfl induced a strong upregulation of XBP1 in all cell types, but with faster kinetics in CNS cells. In contrast, TBEV strain MucAr-HB-171/11 failed to activate the IRE1...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research