Abstract
Rabies is a zoonotic disease caused by the neurotropic rabies virus (RABV). In the absence of treatment the infection is nearly always fatal for the host. Extensive research aimed at better understanding RABV pathogenicity and immunogenicity has led to the characterization of a wide array of RABV strains. Comparative studies between pathogenic and attenuated RABV strains have provided insights into the mechanism by which the virus can be cleared from CNS tissues. In this context, attenuated RABV represents a unique model in which the timely development of an unconventional non-inflammatory rabies-specific neuroimmune response is the key determinant of host survival. Highly pathogenic wild-type rabies viruses have evolved strategies to evade the host immune response and spread through the maintenance of blood-brain barrier integrity and an intact neuronal network. The focus of this review is to provide a synopsis of the differences in the CNS immune responses to pathogenic and attenuated RABV strains and their relevance for the development of new treatment strategies.