The rogue proteins that cause chronic wasting disease (CWD) exhibit a dramatic increase in their infectious nature when bound to common soil particles, according to a new study.
Writing in the journal Public Library of Science (PLoS) Pathogens, a group led by University of Wisconsin-Madison prion expert Judd Aiken reports that prions, the protein agents of a family of fatal brain disorders, bind tightly to a common soil mineral and significantly increase the oral transmissibility of the agent.
The finding is important because it may help explain how chronic wasting disease and scrapie persist in the environment and spread efficiently in animal populations.
"We found a huge difference between infectious agent alone and infectious agent bound to these soil particles," says Aiken, the senior author of the new study and a professor of comparative biosciences in the UW-Madison School of Veterinary Medicine. "We observed an almost 700-fold difference" in the rate of infection.
Prions are an abnormal form of a protein produced normally by the body. Tough as nails, they can persist in the environment for long periods of time and retain their infectious capabilities. It is believed that prions may persist in the soil around the carcasses of dead animals and other locations where infected animals shed the protein in body fluids.
"These disease agents can stay out there for years and stay infectious," Aiken explains.
And herbivores such as deer and sheep, which are susceptible to prion infection, tend to consume a fair amount of dirt daily as they graze and forage. They are also known to consume soil as a source of minerals. Mineral licks are frequented by many animals, raising the prospect that the agents may become concentrated in the soil.
Relatively little is known about the routes of prion transmission in animals, but the new Wisconsin study may help to resolve one puzzle: Oral transmission of prions, says Aiken, tends not to be very efficient.
"This is a dichotomy in our field, and maybe (the new research) is part of the answer."
In their studies, the Wisconsin researchers looked at the ability of prions to bind to different types of common soil minerals. One, known as montmorillonite, is a type of clay and prions seem to have a special affinity for latching onto the microscopic particles.
"We expected the binding of the montmorillonite to be the highest among the minerals we examined. However, we were surprised by the strength of the binding," notes Joel Pedersen, a UW-Madison professor of soil science who helped direct the new study.
The Wisconsin team also looked at the ability of the prion to bind to two other common soil minerals: quartz and kaolinite, another common clay mineral.
"We found binding of the abnormal protein to all three," says Aiken, "but the binding to montmorillonite was very avid, very tight. We found it very difficult to remove the prions from the montmorillonite."
Feeding the prion-mineral mix to hamsters, a common animal model for prion disease, Aiken's team expected to see a lower rate of infection than animals dosed with pure agent. Surprisingly, prions bound to montmorillonite were significantly more infectious than prions alone.
"We thought the binding might decrease infectivity," Aiken explains. "In each case, you add montmorillonite and we get more animals sicker and quicker than in the absence of montmorillonite clay."
What is occurring in soils in the woods and on the farm is unknown, says Pedersen, but the new findings may help begin to answer some key questions about how prions survive in the soil and retain their infectious nature, sometimes for years.
In the case of scrapie, the prion disease of sheep, observations of sheep pastures in the United Kingdom and Iceland have shown that animals introduced into pastures that once held infected animals could become infected. Infectivity of prions was also enhanced when they were bound to whole soil.
"Since the 1940s it's been known that 'infected pastures' have the ability to infect new animals," according to Aiken.
Pedersen notes that soils are a complex mixture of organic and inorganic components that vary across the landscape and that scientists are just beginning to tease out factors in soils that may contribute to transmissibility. The new study implies, he says, "that some soils may promote the transmission of the prion agent more readily than others."
Why that's the case is unknown, Pedersen explains, but the Wisconsin team is exploring several hypotheses: that the soil particles might somehow protect the prion from degradation in the digestive system, that prions bound to clay might change the route or degree of uptake of the agent, or that the mineral somehow alters the size of prion aggregates, which have been shown to be more infectious than prions alone.
Aiken emphasizes there's still much to learn about routes of prion transmission, and the role of soil is just beginning to be explored.
"Soil is a very complex medium and we don't know what the agent is binding to" in natural or agricultural settings, Aiken says. "We do know that soil is not the only way it transmits. Animal-to-animal transmission is important, too."
In addition to Aiken and Pedersen, authors of the PLoS Pathogens paper include Christopher J. Johnson, Rick J. Chappell and Debbie McKenzie. The work was supported by a grant from the U.S. Department of Defense.
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