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.

TBEV can be categorized into European, Siberian, and Far Eastern subtypes according to phylogenetic differences. The Siberian and Far Eastern subtypes have been associated with more severe disease compared to the European subtype [57, 58] . Increased pathogenicity could be due to several factors, e.g., ability to interfere with the type I IFN response. Therefore, viral growth of two reference strains; the Siberian Aina and Far Eastern Sofjin, was analyzed in WT and IFNAR −/− astrocytes (Fig. 2c, d) . Similar to the European subtype of TBEV, an interferon response also restricted the spread of Siberian and Far Eastern TBEV subtypes (Fig. 2c, d) . Although the type I IFN response plays an important role in mosquito-borne neurotropic flavivirus (WNV, JEV, and ZIKV) infections in vivo [12-14, 59, 60] , the specific role of IFNAR signaling in restricting viral growth in astrocytes is unknown. WT and IFNAR −/− astrocytes were infected with JEV, WNV, and ZIKV, and the numbers of infected cells were determined ( Fig. 2e-g) . For all three mosquito-borne viruses, the IFN response was required for the restriction of viral spread in astrocytes. Our data shows that the type I IFN response in astrocytes efficiently restricts the spread of both tick-and mosquito-borne neurotropic flaviviruses.