Factors involved in the progression of JE infection from sub-clinical disease to fatal encephalitis are yet to be fully deciphered. Although the immunological components of protection in the host have been extensively studied, cellular and molecular pathways of JE infection are yet to be understood. Differential ex-pression (DE) profiling of genes using high throughput system enables the study of complex interaction of pathways involved. In this study, early changes in gene ex-pression in the brains of 2-week-old mice, upon lethal infection with Japanese encephalitis virus, were analyzed. The down regulatory (DR) profile includes the genes coding for IL-3, IL-4, IL5, TGFâ, Bcl2 and GMCSF. Whereas, TNFá, Stat1, 2, 5a, NfêB, PDGF and IFN-ã are all upregulated (UR). The adipocytokine pathway up regulation explains the increased ex-pression of TNFá through the up regulation of TNFrs1a and 1b. IL-3 and GM CSF are known to inhibit TNFá. However, in this situation IL-3 is down regulated, which possibly explains the increased ex-pression of TNFá. IL-3 deprivation indicates cell death and decreased ex-pression of Bcl2 also indicates the apoptotic activity involved with neuronal degeneration. The Stats are activated after stimulation of the PDGF receptors and c-kit, which are all up regulated in the present condition. Stat1 through Stat5 are transcription factors involved in the Interferon response pathway. The increased ex-pression of the IFNã explains the up regulatory activity of the Stats. IFNã inhibits IL-4 and IL-5, the immunodulatory cytokines indicating a Th1 type of response.
