other soluble factors such as neurotoxins, excitatory neurotransmitters, prostaglandin, reactive oxygen, and nitrogen species are secreted by activated microglia. In a murine model of JE, it was found that in the hippocampus and the striatum, the number of activated microglia was more than anywhere else in the brain, closely followed by that in the thalamus. In the cortex, the number of activated microglia was significantly less when compared to other regions of the mouse brain. An overall induction of differential expression of proinflammatory cytokines and chemokines from different brain regions during a progressive Japanese encephalitis infection was also observed. Although the net effect of the proinflammatory mediators is to kill infectious organisms and infected cells as well as to stimulate the production of molecules that amplify the mounting response to damage, it is also evident that in a nonregenerating organ such as the brain, a dysregulated innate immune response would be deleterious. In JE the tight regulation of microglial activation appears to be disturbed, resulting in an autotoxic loop of microglial activation that possibly leads to bystander neuronal damage. In animals, key signs include infertility and abortion in pigs, neurological disease in horses, and systemic signs including fever, lethargy and anorexia. Cause It is a disease caused by the mosquito-borne Japanese encephalitis virus (JEV). Virology JEV is a virus from the family Flaviviridae, part of the Japanese encephalitis serocomplex of 9 genetically and antigenically related viruses, some which are particularly severe in horses, and four known to infect humans including West Nile virus. The enveloped virus is closely related to the West Nile virus and the St. Louis encephalitis virus. The positive sense single-stranded RNA genome is packaged in the capsid which is formed by the capsid protein. The outer envelope is formed by envelope protein and is the protective antigen. It aids in entry of the virus into the cell. The genome also encodes several nonstructural proteins (NS1, NS2a, NS2b, NS3, N4a, NS4b, NS5). NS1 is produced as a secretory form also. NS3 is a putative helicase, and NS5 is the viral polymerase. It has been noted that Japanese encephalitis infects the lumen of the endoplasmic reticulum (ER) and rapidly accumulates substantial amounts of viral proteins. Based on the envelope gene, there are five genotypes (I–V). The Muar strain, isolated from a patient in Malaya in 1952, is the prototype strain of genotype V. Genotype IV appears to be