Molecular Mechanism and Role of Japanese Encephalitis Virus Infection in Central Nervous System-Mediated Diseases
Pardeep Yadav,
Pratik Chakraborty,
Niraj Kumar Jha,
Saikat Dewanjee,
Abhimanyu Kumar Jha,
Siva Prasad Panda,
Prabhu Chandra Mishra,
Abhijit Dey,
Saurabh Kumar Jha
Affiliations
Pardeep Yadav
Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Room # 311, Block-01, Plot No. 32–34, Knowledge Park III, Greater Noida 201310, India
Pratik Chakraborty
Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India
Niraj Kumar Jha
Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Room # 311, Block-01, Plot No. 32–34, Knowledge Park III, Greater Noida 201310, India
Saikat Dewanjee
Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India
Abhimanyu Kumar Jha
Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Room # 311, Block-01, Plot No. 32–34, Knowledge Park III, Greater Noida 201310, India
Siva Prasad Panda
Pharmacology Research Division, Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
Prabhu Chandra Mishra
Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Room # 311, Block-01, Plot No. 32–34, Knowledge Park III, Greater Noida 201310, India
Abhijit Dey
Department of Life Sciences, Presidency University, Kolkata 700073, India
Saurabh Kumar Jha
Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Room # 311, Block-01, Plot No. 32–34, Knowledge Park III, Greater Noida 201310, India
The Japanese encephalitis virus (JEV) is the most common cause of neurodegenerative disease in Southeast Asia and the Western Pacific region; approximately 1.15 billion people are at risk, and thousands suffer from permanent neurological disorders across Asian countries, with 10–15 thousand people dying each year. JEV crosses the blood-brain barrier (BBB) and forms a complex with receptors on the surface of neurons. GRP78, Src, TLR7, caveolin-1, and dopamine receptor D2 are involved in JEV binding and entry into the neurons, and these receptors also play a role in carcinogenic activity in cells. JEV binds to GRP78, a member of the HSP70 overexpressed on malignant cells to enter neurons, indicating a higher chance of JEV infection in cancer patients. However, JEV enters human brain microvascular endothelial cells via an endocytic pathway mediated by caveolae and the ezrin protein and also targets dopamine-rich areas for infection of the midbrain via altering dopamine levels. In addition, JEV complexed with CLEC5A receptor of macrophage cells is involved in the breakdown of the BBB and central nervous system (CNS) inflammation. CLEC5A-mediated infection is also responsible for the influx of cytokines into the CNS. In this review, we discuss the neuronal and macrophage surface receptors involved in neuronal death.
