In silico study identifies hub genes and regulatory network associated with the pathogenesis of Japanese Encephalitis Virus

Abstract Japanese encephalitis (JE) is a mosquito-borne viral disease caused by the Japanese encephalitis virus (JEV). Approximately 3 billion people from South-East Asia are at risk of this disease; however, the pathogenesis mediated by this virus is still elusive. Therefore, this study was undertaken to identify hub genes and regulator network associated with JE pathogenesis using several computational tools. Our data revealed VEGFA and WNT5A genes as major contributing factors for the development of primary stage of invasive JEV. These two genes were found to be regulated by transcription factor and miRNA targets from multiple databases. The analysis revealed that the activation of VEGFA and WNT5A is mediated by several transcription factors that include EGR1, EPAS1, ETS1, FOS, HIF1A and GLI3, GLI2, GLI1, respectively. Furthermore, we also identified several miRNAs that regulates the repression of VEGFA and WNT5A and also measured their seed pairing and binding free energy of gene-miRNAs interactions. The mathematical modelling supports the role of above mentioned miRNAs in the initiation of the regulatory pathogenesis in JEV. Additionally, we have shown that the type 1 and type 2 coherent and incoherent feed forward loops help to determine the VEGFA gene regulation by TFs and miRNAs. Altogether, this study demonstrates the regulation of JEV pathogenesis by WNT5A/VEGFA and associated miRNAs.