Molecular Mechanisms of Raccoon Rabies Virus Progression in Its Natural Host

Abstract

Rabies virus presents a global public health problem. Our current understanding of the molecular determinants of rabies virulence stems from rodent models and laboratory strains of the virus, however, it is unclear how well rodent models represent viral response in natural reservoirs. Here, we examined interactions between the raccoon variant of rabies virus (RRV) and its natural host, raccoons, to gain a better understanding of molecular determinants of virulence in this system. We found expression patterns of RRV genes under tight control until the virus reached the central nervous system where replication increased significantly. Further, our examination of viral variants within an individual revealed that variant diversity may have an effect on virulence. We found that a mutation at a region of a T helper cell epitope on the nucleoprotein was associated with viral challenge outcomes and could be associated with RRV pathogenicity.