Fast type I interferon response protects astrocytes from flavivirus infection and virus-induced cytopathic effects

Lindqvist, Richard; Mundt, Filip; Gilthorpe, Jonathan D.; Wölfel, Silke; Gekara, Nelson O.; Kröger, Andrea; Överby, Anna K.

Predicting upstream regulators responsible for the different expression patterns in IFNAR −/− -, supernatant-, and IFNαB/D-treated astrocytes identified type I IFN as well as IFN signaling molecules to have the highest activation scores. Similar findings were found in a previous study where IFN signaling and antiviral mediators were among the most upregulated pathways and genes in WNV-infected mice brains [51] . IFNγ-STAT1-IRF-1 signaling cascade was predicted as an upstream regulator both in supernatant and IFNαB/D-treated astrocytes. Although IFNγ transcripts were not detected in TBEV infected, astrocytes IRF-1 could be directly induced by virus infection and could be responsible for the induction of the overlap between inducible genes among the type I and II IFNs [79, [82] [83] [84] . Taken together, the RNAseq confirms the potent IFN response of the astrocytes and identifies a subset of genes as key players in determining the outcome of TBEV infection in astrocytes.