The Battle Between Japanese Encephalitis Virus and Host Innate Immune System: Evasion and Response

Japanese encephalitis (JE) is a natural zoonotic disease caused by the Japanese encephalitis virus (JEV), which poses potential threats to human health and the pig farming industry. To establish infection, JEV must overcome the innate immune responses and complete its lifecycle in new hosts. Notably, the direct virus-induced neuronal cell death and an uncontrolled neuroinflammatory response jointly lead to the pathogenesis of JEV. In this review, we will focus on the innate immune response to JEV infection and the viral immune evasion strategies, such as escaping recognition or inhibiting the production of antiviral factors. Generally, JEV exploits four innate immune pathways, including type I interferon, interleukins, programmed cell death, and autophagy, to facilitate self-replication or exacerbate disease. Moreover, host microRNAs modulated during JEV infection have emerged as key regulators of this virus–host interplay. Therefore, a full understanding of how the immune system reacts to JEV infection and how the virus evades innate immune clearance will help develop effective vaccines or antiviral therapies.