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 SAi4-14-2, 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 SA14-14-2 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. Thus, these findings elucidate the molecular basis of the neurovirulence caused by JEV and other closely related encephalitic flaviviruses, a major step in understanding their neuropathogenesis. From a clinical perspective, the discovery of the viral neurovirulence factor and its role will have direct application to the design of a novel class of broad-spectrum antivirals to treat and prevent infection of JEV and other taxonomically related neurotropic flaviviruses.La présente invention concerne un groupe de flavivirus transmis par les moustiques qui provoquent lencéphalite mortelle chez les hommes, et comptent parmi les principaux agents pathogènes humains dimportance globale. Ce groupe comprend le virus de lencéphalite japonaise, le virus du Nil occidental, le virus de lencéphalite de Saint Louis, et le virus de lencéphalite de la vallée de Murray. Dans la présente invention, le premier système de génétique inverse a été développé pour SAi4-14-2, un vaccin vivant contre lencéphalite japonaise qui est communément utilisé dans la plupart des zones endémiques de lencéphalit
