Research Projects

Japanese encephalitis virus (JEV) is a flavivirus that is spread by mosquitos and is found in numerous nations in Asia, the Western Pacific, and northern Australia. The prevalence of JEV infections in India is slowly increasing, covering around 24 states (1,2). The virus is a prominent cause of epidemic viral encephalitis targeting the central nervous system (CNS). The blood-brain barrier (BBB) of the host acts as a primary structural and functional blockade for viral invasion in the brain and governs the pathogenicity of the virus. Appallingly, despite the known significance of the BBB in JEV infections, there is still a research gap in linking the BBB integrity and JEV infections. Very recently, we have demonstrated that environmental concentrations of dietary emulsifiers/heavy metals affect the tight junctions of the intestine in a mouse model via downregulation of the Wnt pathway (3). Our preliminary studies showed that the integrity of the BBB was also affected by the exposure to dietary emulsifiers (Polysorbate 80-P80/Carboxy methyl cellulose-CMC). We observed significant downregulation of the canonical Wnt/β-catenin pathway in the brain tissue of P80/CMC-exposed mice or primary hippocampal neuronal cells. Furthermore, the tight junction proteins Zonula occludens (ZO1), Occludin (OCC), Claudin (CLN1) were also downregulated in P80-exposed mice. To further corroborate these results, the BBB permeability was also found to be compromised in P80-exposed mice using Evans Blue. The preliminary data is included in the relevant section of the proposal. In this project, we propose to study the effect of a weakened blood-brain barrier (BBB) on susceptibility to Japanese Encephalitis Virus (JEV) infection. We will examine whether in utero exposure to dietary emulsifiers leads to BBB disruption in offspring. Additionally, we will assess whether dietary emulsifiers influence the susceptibility of neuronal cells (N2a, SH-SY5Y, and primary hippocampal neurons) to JEV infection by modulating the host factors. We will also investigate the therapeutic potential against JEV infection by using lithium chloride—a known activator of the canonical Wnt signaling pathway and modulator of Toll-like receptors—using a mouse model. Furthermore, we will investigate the impact of in utero exposure to dietary emulsifiers on the canonical Wnt/β-catenin signaling pathway and immunomodulation in the brains of offspring.