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.

Astrocytes are the most abundant glial cell type in the brain and an important source of type I IFN during various neurotropic viral infections [18, 22, 23] . To investigate the importance of type I IFNs for astrocyte function in neurotropic flavivirus infection, primary astrocytes were isolated from wild-type (WT) and IFNAR −/− mice. These were infected with TBEV strain Hypr at a MOI of 0.1 and analyzed by immunofluorescence (Fig. 1a) . Both WT and IFNAR −/− infected astrocytes expressed the characteristic marker glial fibrillary acidic protein (GFAP) and were found positive for TBEV E (Fig. 1a) . Viral replication was analyzed over time, and low viral titers and replication were observed in WT astrocytes. In contrast, TBEV titers and RNA replication increased dramatically in IFNAR −/− astrocytes over time (Fig. 1b, c) . Infection was also analyzed in MEFs where an unrestricted growth profile was observed in both WT and IFNAR −/− cells (Fig. 1d , e). Our results indicate that IFNAR restricts TBEV replication in a cell type-dependent manner.