Research Projects

Japanese encephalitis virus, a vector-borne virus, is mainly prevalent in Southeast Asia, Japan, China, and India. The dire consequence due to Japanese Encephalitis virus infection is neuropsychiatric sequelae in young humans. No dreadful signs and symptoms are observed in pigs, except piglets from infected sows. However, the virus multiplies significantly in pigs compared to humans, making pigs the amplifier hosts, and humans, the dead-end hosts. Several studies are being conducted to identify host factors or viral factors that act as antivirals or provirals for JEV in different in vitro and in vivo models with no clues on the varied level of viremia between both the hosts- pigs and humans. Hitherto, our previous study showcased host factors like MIF, VMP1, ssc-miR-133a-3p and hsa-miR-3614-5p in maintaining the distinct pattern of JEV growth in human macrophages (THP-1) and pig macrophages (3D4/31) through miRNomics and proteomics. In addition to the findings, there may be several other epitranscriptome/RNA modifications influencing the JEV pathogenesis in human and Pig. Ongoing research on epitranscriptome/RNA modifications, reflects their significant role in regulating the translation and transcription of both host and viral RNA and can be the key determinants in viral growth. Therefore, determining epitranscriptomic signatures in host and viral RNA will help in deciphering the factors responsible for the paradoxical JEV growth in different hosts. To achieve this goal, in this study, RNA modifications associated with the host and viral RNA vis – a – vis JE infection in Pig and Human will be identified and validated. Initially, RNA modifications (m6A) in macrophages, the initial site of JEV replication, in both the amplifier host (Pig) and dead-end host (Human) will be decoded through MeRIP-seq or Direct RNA sequencing by Oxford nanopore technologies. Later, these signatures will be validated through CRISPR/dCas13 and site-directed mutagenesis to confirm their implication on viral kinetics and host responses. Upon achieving these objectives, RNA modifications and their significance in driving distinct host responses, will be elucidated to contribute significantly to understand the pathobiological differences between pigs and humans. The results would pave way to design specific host-directed therapeutics for control and eradication of JE.