Evolutionary Virology May Clarify How Rabies Infects New Hosts

A recent study of the rabies virus genome shows that two major subgroups of rabies virus, bat-related rabies and dog-related rabies, evolved in different ways. Humans probably had a hand in spreading dog-related rabies virus worldwide, according to a report in PLOS Pathogens, and the virus may require only minimal adaptive evolution to jump to new host species.

Most emerging infectious diseases in humans are zoonotic in origin, but the evolutionary factors that drive jumps to new species are still unclear, say the authors. “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,” they write. “Revealing how viruses jump species boundaries and establish productive infections in new hosts is key to understanding disease emergence.”

The rabies virus is maintained in host species in the orders Chiroptera (bats) and Carnivora but can cause disease in many other mammal species. Bat-related rabies virus affects bats, skunks, and raccoons in North and South America. Dog-related rabies virus affects dogs worldwide and wild carnivores in specific geographic regions (like foxes in the Middle East and ferret-badgers in Asia).

The investigators analyzed 321 rabies virus genome sequences collected from 66 countries over 65 years. One hundred fifty-one sequences were already stored in GenBank; the researchers sequenced another 170 genomes archived at the Institut Pasteur in Paris, France. Most previous phylogenetic studies of the rabies virus did not use the entire genome and were limited to certain geographic areas or host species, they note.

When the researchers analyzed the sequences’ mutation rates, they found that changes in the bat-related rabies virus genome did not correlate with time. This means, they say, that bat-related rabies viruses have not evolved uniformly. Mutation rates of dog-related rabies viruses, however, did correlate with time, allowing the investigators to use regression analysis to estimate dates of divergence from common ancestors.

The results show that humans may have facilitated the worldwide spread of rabies virus. The earliest surviving lineages of dog-related rabies virus date back to 1308 to 1510, which coincides with the development of large-scale international trade networks, say the authors. “The concomitant dissemination of RABV [rabies virus] during this period, probably by dogs travelling by boats with their owners, therefore provides a powerful example of the early human-mediated dissemination of a zoonotic disease.”

One central question in evolutionary virology, according to the authors, is why some viruses are better able than others to jump to new species. Their results show that the virus is more likely to jump from dogs to other species than from other species back to dogs. However, whether host shifting is facilitated by adaptive evolution on the part of the rabies virus—or simply a matter of chance—is still unclear. The analysis did show that positive selection was not likely involved in virus mutation in Asian ferret-badgers, in which the virus evolved twice as fast as in dogs.

“Successful cross-species transmission is a complex ecological and evolutionary process, beginning with exposure and contact between the two species, followed by the successful infection of the new host species, and potentially host-adaptive evolution to enable long-term sustained transmission,” conclude the authors. The rabies virus may need to undergo only subtle adaptive evolution to infect new species, they write.

Dr. Laurie Anne Walden received her doctorate in veterinary medicine from North Carolina State University. After an internship in small animal medicine and surgery at Auburn University, she returned to North Carolina, where she has been in small animal primary care practice for over 20 years. Dr. Walden is also a board-certified editor in the life sciences and owner of Walden Medical Writing, LLC. She works as a full-time freelance medical writer and editor and continues to see patients a few days each month.