Japanese Encephalitis: A Tale of Inflammation and Degeneration in the Central Nervous System

Abstract

Over more than a century, many regions in Southeast Asia have been under the grip of a disease called Japanese encephalitis, which is caused by a vector-borne flavivirus. The origins of the disease can be traced to the frequent and multiple epidemics in the islands of Japan during the early twentieth century, which then rapidly spread to other countries. Currently, an estimated three billion people live in the JE endemic region, making this one of the most dreaded arboviral diseases. The JE virus is highly neuroinvasive, and once it reaches the central nervous system, it replicates rapidly in neurons and ultimately causes death. This initiates an inflammation cascade involving the glial cells which further complicates matters in the brain. The virus can specially arrest cell cycle in neuroprogenitor cells, thereby inhibiting their maturation. All these features cause debilitating symptoms and can be fatal in children. Survivors generally suffer from various neuropsychiatric sequelae and require prolonged rehabilitation measures to regain normalcy. There is no specific antiviral therapy available. To date, all therapeutic countermeasures have been supportive. Even though vaccination has led to a marked decrease in the incidence of this disease in several countries in the endemic zone, still epidemics of varied proportions are reported almost every year. In this chapter, our efforts have been focused on providing a general idea about the virus, a detailed analysis of the pathology of the disease, an insight into basic research in unraveling the molecular mechanisms of host responses, and a brief idea about the multiple efforts made over the years to find a cure for the disease.