Figure 1. Innate immune response triggered by flavivirus infection, highlighting mouse genes involved in susceptibility or resistance.

Following infection by a flavivirus, viral RNA is detected by TLRs and RLRs which induce activation of several transcription factors such as NF-κB and IRFs which, in turn, promote the transcription of type I, type II and type III IFNs. Once secreted, each IFN subtype (α/β, γ, λ) binds to its specific receptor (IFNAR, IFNGR, IFNLR) which leads to the activation of the JAK/STAT transduction pathways. IFNAR and IFNLR both signal through STAT1, STAT2 and IRF9 whereas only STAT1 is activated by IFNGR. STAT proteins activate the transcription of hundreds of ISGs, including Oas genes, some of which sense viral dsRNA and further promote viral ssRNA cleavage by activating RNase L. Genes of the IFN signaling pathway identified in the mouse as host genetic factors of susceptibility to flaviviral infections are depicted in red.

Abbreviations: TLR, Toll-like receptor; RLR, RIG-I-like receptor; IFN, interferon; IRF, IFN regulatory factor; ISG, IFN stimulated gene; ssRNA, single-stranded RNA; dsRNA, double-stranded RNA.