The spread and evolution of rabies virus: conquering new frontiers

Much of the molecular virology of rabies virus has been well characterized, and we are gaining a better understanding of how infection dynamics and immune status relate to transmission. In this Review, Schnell and colleagues explore rabies virus transmission, enzootic maintenance and epizootic spread, as well as molecular evolutionary dynamics, host adaptation and the origins of rabies virus. Rabies is a lethal zoonotic disease that is caused by lyssaviruses, most often rabies virus. Despite control efforts, sporadic outbreaks in wildlife populations are largely unpredictable, underscoring our incomplete knowledge of what governs viral transmission and spread in reservoir hosts. Furthermore, the evolutionary history of rabies virus and related lyssaviruses remains largely unclear. Robust surveillance efforts combined with diagnostics and disease modelling are now providing insights into the epidemiology and evolution of rabies virus. The immune status of the host, the nature of exposure and strain differences all clearly influence infection and transmission dynamics. In this Review, we focus on rabies virus infections in the wildlife and synthesize current knowledge in the rapidly advancing fields of rabies virus epidemiology and evolution, and advocate for multidisciplinary approaches to advance our understanding of this disease.