A group of mosquito-borne flaviviruses that cause fatal encephalitis in humans is among the most important of all emerging human pathogens of global significance. This group includes Japanese encephalitis virus (JEV), West Nile virus, St. Louis encephalitis virus, and Murray Valley encephalitis virus. In the present disclosure, the first reverse genetics system has been developed for SA14-14-2, a live JE vaccine that is most commonly used in most JE-endemic areas, by constructing an infectious bacterial artificial chromosome that contains the full-length SA14-14-2 cDNA. Using this infectious SA 14-14-2 cDNA, combined with a mouse model for JEV infection, a key viral neurovirulence factor has been discovered that is a conserved single amino acid in the ij hairpin adjacent to the fusion loop of the viral E glycoprotein, which regulates viral infectivity into neurons within the central nervous system.
