The spread and evolution of rabies virus: conquering new frontiers

Key Points With much of the molecular virology characterized, we are now gaining an appreciation of how nuanced rabies virus infection dynamics are and how immune status relates to transmission. The growing number of recognized rabies virus-related lyssaviruses highlights shortcomings in our discriminatory diagnostics and raises questions about their impact on human health. The lack of therapeutics for some of these lyssaviruses is a major concern. Enzootic maintenance of rabies virus within a population depends on transmission within narrow windows. The virus avoids extinction by both general and reservoir host-specific mechanisms with remarkable epidemiological plasticity. Features of rabies virus biology, ecology and evolution have made the virus a model pathogen for disease ecology and evolution. Recent work using mathematical models and phylodynamic analyses have enabled reconstruction and forecasting of epizootic spread of the virus at the landscape level. At an evolutionary level, there is evidence that strong barriers prevent rabies virus from establishing in new host species, and both ecological opportunities and viral adaptation are needed to overcome these barriers. Studies of rabies virus molecular evolutionary dynamics have revealed the role of purifying selection and the importance of viral and host genetic backgrounds in host shifts. Further study of contemporary host shifts will likely shed light on the unknown origin of rabies. We suggest that efforts be focused on developing strategies and technologies to manage rabies viruses within bat reservoirs as previously done with carnivores, integrating diagnostics that can rapidly differentiate strains into surveillance efforts, honing our predictive power to detect outbreaks and coordinating local resources to halt the spread of this lethal zoonosis.