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.

Previous studies have indicated the importance of astrocyte-produced IFN in various viral infections [18, 22, 23] . The observed differences in the impact of IFNAR on astrocytes and MEFs could either be explained by the ability to respond to, or the capacity to induce, IFN following infection. To determine the impact of the type I IFN response in the overall antiviral response, astrocytes and MEFs were pretreated with IFNαB/D [49] Sixteen hours before TBEV infection (Fig. 3a, b) . TBEV growth was inhibited to a similar extent showing that both cell-types were able to mount a strong antiviral response upon IFN treatment. Thus, the ability to respond to IFN (Fig. 3a, b) could not explain the lack of control of viral replication in IFNAR −/− MEFs (Fig. 1d, e) . To test whether astrocytes and MEFs differ in their capability to induce type I IFNs after infection, IFNβ and IFNα2 mRNAs were quantified by realtime qPCR (Fig. 3c, d) . Interestingly, the IFN responses in the two cell types were quite different. Whereas astrocytes induced IFN mRNA after 6 h, the response in MEFs was delayed and IFNβ and IFNα2 mRNAs were detected only after 24 or 48 hpi, respectively. Next, a VSV-GFP-based . Asterisks indicate data were statistically significant: ***p < 0.0001 bioassay on MEFs was applied to quantify secreted IFN, and astrocytes were found to secrete higher levels of IFNs 24 hpi compared to MEFs (Fig. 3e) . These data indicate that astrocytes react to viral infection by the induction of IFNs much more rapidly than MEFs.