Differential expression pattern of host inflammasome genes in Japanese encephalitis virus infected patients

Abstract

Background: Japanese encephalitis virus (JEV) causes one of the deadliest viral encephalitis in Asia and presents clinical manifestations ranging from asymptomatic to severe neurological symptoms and even death. Post infection, anti-viral response is induced by inflammasome complexes via NFκB and Jak/Stat signalling. However, there is limited knowledge on the expression levels of inflammasomes among JEV infected patients. Therefore, to understand the disease pathogenesis, we analysed the expression pattern of inflammasome genes among mild and severe JE cases. Methods and materials: Gene expression levels of inflammasome complex (Caspase 1, Pycard and NLRP3) was assessed in peripheral blood mononuclear cells (PBMCs) among mild and severe JE patients (n = 19) as well as in healthy individuals (n = 19). RNA extraction and cDNA synthesis were performed as per the manufacturer's guidelines. mRNA expression levels were quantified using real-time PCR. Results: The present study demonstrated that Caspase 1, Pycard and NLRP3 were down-regulated by log 0.14, 0.40 and 0.54-fold respectively among mild JE cases as compared to controls. On the other hand, Caspase 1, Pycard and NLRP3 genes were upregulated by log 0.79, 0.96 and 0.92-fold respectively in severe JE cases as compared to controls. Among the inflammasomes, gene expression of Pycard was significantly elevated in severe JE cases in comparison to the mild cases (p < 0.05). Conclusion: Our findings corroborate the potential activation of inflammasome pathway during JEV infection. The down regulation of the inflammasome genes among mild JE cases may indicate a protective role during the initial phase of infection. However, at a later stage, the genes may contribute to the adverse pathogenesis of the disease. In conclusion, the present study proposes that the variation in gene expression of inflammasomes may be associated with magnitude of JE pathogenesis and could be used as a probable marker for JE severity.