Arctic fox rabies has evolved to remain in place

Arctic fox rabies has evolved to remain in place

New research suggests that rabies has evolved to make infected arctic foxes more aggressive, increasing the likelihood that the deadly virus will spread through biting and survive in the sparsely populated species.

That contrasts with raccoons, a rabies host with much higher population density and therefore needing less-drastic behavioral changes for the virus to spread.

The research into both species, led by veterinary medicine professor Karsten Hueffer of the University of Alaska Fairbanks College of Natural Science and Mathematics, offers new insight into how viruses adapt to the behavior and biology of different animal species.

"It's always difficult and dangerous to inject a purpose, especially into a virus," Hueffer said. "They clearly have no brain, but the virus has evolved to change the animal's behavior so it favors transmission."

The research was published Oct. 22 in Proceedings of the National Academy of Sciences.

Rabies is nearly always fatal after symptoms start, even in humans. After infection, the rabies virus travels through the nervous system to the brain. In humans, that process can take weeks or months before symptoms appear, according to the U.S. Centers for Disease Control and Prevention. Medical treatment prior to the onset of symptoms is nearly 100% effective.

In arctic foxes, the virus must continually spread to maintain a stable presence. Rabies is unusual among viruses because it spreads primarily through biting.

"We have endemic rabies that is maintained in arctic foxes," Hueffer said. "That animal probably has to be really aggressive to make sure that virus spreads because there's not many neighbors around. It's not going to meet very many arctic foxes."

Understanding how rabies evolves and spreads in the Arctic can help scientists understand virus behavior elsewhere.

"If we understand how this extreme virus works in extreme ends, we can probably understand something about rabies and about how infectious diseases in general work," Hueffer said.

Researchers used computer modeling to compare how rabies spreads among arctic foxes and raccoons, which carry different variants of the virus and have different population levels.

Arctic foxes occupy tundra, coastal areas and sea ice in Alaska and throughout the circumpolar North. They have a population density of fewer than one animal per 2 square kilometers.

Raccoons, which also spread rabies through biting, commonly have a density of 10 or more animals per square kilometer. They're common across much of North America, but their density and the related level of aggressiveness varies greatly depending on whether the population is urban, rural or boreal and mountainous.

To become established in a population, the rabies virus must spread often enough to replace infections that end when infected animals die. But if it spreads too rapidly, it can kill so many susceptible animals that the virus can no longer sustain itself.

The new research builds on work by Hueffer and others, published in 2017, that identified a possible way rabies changes the behavior of infected animals.

The virus has proteins called glycoproteins on its outer surface. A small section of one of these proteins resembles certain snake toxins and can interfere with receptors that help nerve cells communicate.

The new research found that the snake toxin-like portion from the arctic fox virus variant was especially effective at interfering with a type of nerve-cell receptor involved in regulating behavior. It was more effective than the same portion of the protein from raccoon rabies variants.

Researchers also found that many of the genetic changes potentially involved in the virus's adaptation to arctic foxes and raccoons occurred in this same section of the protein.

The work suggests a possible explanation for how the virus influences aggression and increases the likelihood of biting.

"Raccoons don't want to be too aggressive because the virus would kill all the raccoons," Hueffer said. "Arctic foxes don't want to be too mild, because then there wouldn't be enough transmission because there aren't enough arctic foxes on the landscape."

In Alaska, the southern part of the arctic fox range overlaps with that of red foxes, which are widespread in the state but do not maintain their own rabies variant. Arctic fox rabies can spread to red foxes and other animals, but it generally does not become established in those populations.

"There isn't enough time for the virus to adapt to a new host before it fizzles out," Hueffer said.

The research paper's UAF co-authors include professor John Rhodes of the Department of Mathematics and Statistics, graduate student Brittany O'Brien and associate professor Maegan Weltzin. O'Brien and Weltzin are both affiliated with the Department of Chemistry and Biochemistry and the Institute of Arctic Biology.

ADDITIONAL CONTACT: Karsten Hueffer, [email protected]

075-27