Flavivirus encephalitis: Immunopathogenesis of disease and immunomodulation

Abstract

Neurotropic flaviviruses are transmitted by arthropod vectors largely in an enzootic cycle that frequently involves humans incidentally. They are perhaps the most widespread of all viruses and continue to pose a threat, with increasing global warming, air travel and the extension of their insect vector habitat due to expanding human activity. Infection by these viruses is associated with a significant immunopathological response in a minority of individuals who, if they survive, may endure permanent neurological sequelae. While universal immunisation remains the ideal to prevent infection, progress has been slow and even available vaccines may not reach target populations. Unfortunately, our understanding of the interaction of these viruses with the mammalian host is still rudimentary, making current treatment approaches to disease at best empirical. However, recently, in addition to inhibition of the immunopathogenic activity of cells in situ, approaches to reducing the massive pathogenic leukocyte immigration into the central nervous system (CNS) have targeted monocytes with significant success in animal models. The universality of this population across a wide spectrum of diseases may enable a finely tuned approach to reducing the pathogenic component in encephalitis without interfering with the generation of immunity.