Rabies, as it exists today, likely crossed the globe at the same time as explorers in the sixteenth century.

While previous studies have determined two major phylogenetic groups existed for rabies—one bat-related and the other dog-related—there has never been a study that looked at global and evolutionary implications. In research published in PLOS Pathogens on Thursday, Dec. 15, Cécile Troupin and other researchers from the WHO Collaborating Centre for Reference and Research on Rabies in Paris, determined two distinct natural evolution patterns for the rabies virus (RABV).

Studying the sequence and evolution of rabies applies to the spread of infection in general, according to the researchers: “Understanding the evolutionary patterns and processes that underpin such cross-species transmission is of importance for predicting the spread of zoonotic infections, and hence to their ultimate control.”

This is particularly important for dog-related RABV, as it can be found worldwide in dogs and other wildlife, including foxes and raccoon dogs in Europe, skunks, foxes, coyotes and mongooses in the Americas, and mongooses in Africa. (In contrast, bat-related RABV is only found in the Americas.) What’s more, dogs are responsible for 99% of human rabies cases, and “are likely the main vector for the inter-species transmission of dog-related RABV.”

The study utilized a data set of 321 whole-genome sequences sampled from 66 countries over a period of 65 years. It is the first phylogenetic study of RABV on a genome-wide and global scale. The size of the data set allowed the researchers to reveal any heterogeneity in evolutionary rates among RABV adapted to different primary hosts, and determine the complex evolutionary dynamics of RABV as it adapts to new hosts.

Ultimately, there was no correlation between time and genetic divergence was found in bat-related RABV, but the evolution of dog-related RABV followed a generally clock-like structure, although with a relatively low evolutionary rate. The data indicate that the establishment of dog-related RABV in new carnivore hosts may only require subtle adaptive evolution.

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