**7. Immune response**

The pathogenesis of the neurotropic flaviviruses like JEV, involves both virus-mediated damage and the host immune responses. After the mosquito bite, when the virus is inoculat‐ ed in the host, it replicates in skin dendritic cells, and then is transported to lymph nodes, from where it spreads to peripheral organs, enhancing the viremia. Entry into CNS is an im‐ portant event which aids viral encephalitis [9]. Roles of both the innate and adaptive im‐ mune responses in controlling flaviviral infection are important. IgM and IgG are involved in preventing viral dissemination to the CNS, however CD8+ T cells are important for recov‐ ery and immunopathological phases of viral infection.

Infection with flavivirus triggers the host's innate immunity, resulting in signalling path‐ ways and production of interferons (IFN) which are secretory cytokines produced as a re‐ sponse against viral infection. When these IFN bind to the cell-surface receptors, Jak–Stat signaling pathway is activated which in turn induces the transcription of interferon-stimu‐ lated genes (ISGs), and the resulting products have potent antiviral, antitumor, and immu‐ nomodulatory effects. To win against the IFN defence system, viruses encode viral proteins which are potent enough to block IFN signaling, via various mechanisms (Sen 2001, Weber et al., 2004) like blocking IFN action by preventing Tyk-2 phosphorylation by the production of NS5 protein of JEV (Lin et al., 2004; Lin et al., 2006;Liang et al., 2009).
