we found very low expression of RIG-I both in whole brain and in cultured neurons. JEV predominantly infects neurons, following which RIG-I was found to be expressed in significantly higher levels in brain. As after inhibiting the virus using an antisense molecule no significant alteration in RIG-I expression was observed from non-infected brain samples, it can be safely assumed that JEV causes upregulation of this PRR in various CNS cell types, including neurons. Upon recognition of viral RNA, the caspase recruitment domain -like motif of RIG-I gets activated and interacts with interferon promoter stimulator-1 to relay the signal. The signal is divided at IPS-1, resulting in activation of NFkB and IRF-3 and -7. Post JEV infection, IPS-1 expression was found to be moderately increased that led to dramatic increase of the adaptor molecule FADD. Apart from its role in apoptotic process, FADD is also known to activate TNF receptor-associated factor 6, which was found to be increased following JEV infection in neurons. TRAF 6 activates IkB kinase a/b via Tak1 leading to phosphorylation of IkBa-NFkB complex. JEV infection leads to decreased level of IkBa, at later time point indicating its dissociation from the complex followed by proteolytic degradation. Since the removal of the inhibitory effect of IkBa, NFkB is activated and translocated into the nucleus to modulate the expression of proinflammatory cyto/chemokine genes. We found increased level of phospho NFkB in Ocinaplon neuronal cells following JEV infection. Its level in nuclear extract of these cells was also increased. Activation of p38MAPK has been shown to be associated with the activation of RIG-I via TRAF 2-TAK 1 dependent pathway in non-neuronal cells. Whether this also occurs in neurons was previously unknown. Here we have shown for the first time that following JEV infection, phospho p38MAPK levels are significantly increased in neurons as evident from immunocytochemical observations and also from immunoblot analysis of nuclear extracts obtained from infected cells. Both NFkB and p38MAPK are well known stimulators of proinflammatory cyto/chemokine gene expression, and their upregulation was concurrent with elevated secretions of IL-12, TNF-a, MCP-1 and IL-6 and increased expression of CXCL-10, GMCSF from infected neuronal cells. RIG-I inhibition carried out by transfecting cells with rMO resulted in downregulation of phosphoIKKab, TRAF 6, IPS-1, FADD, and active Caspase 8, except IkBa, which showed significant increase indicating its inhibitory effects on NFkB. OB 24 hydrochloride Subsequently, it was observed that phospho NFkB and phospho p38MAPK levels were decreased that led to reduction in the levels of the proinflammatory mediators. An interesting observation was that neuronal survivability was negatively affected following RIG-I inhibition.