‘Shape-shifting’ prions pose human health risk
NEW CLUES ABOUT DISEASE THAT EATS HOLES IN BRAINS Proteins mutate through food chain, U of A researcher says
Subtle differences in prion proteins can make them more susceptible to mutate into mad cow prions or chronic wasting prions when they pass from one animal to another, potentially putting humans more at risk, says a neurologist and researcher at the University of Alberta.
Valerie Sim, who diagnoses humans with the rare and fatal prion brain disease called Creutzfeldt Jakob disease, discovered in lab models how two subtle differences in the prion protein make it more likely to mutate or adapt when it is exposed to different types of prions. Deer with adaptable prions of chronic wasting disease might more easily transmit disease through their saliva, urine or dung to other species such as moose, sheep, elk or cows, even cats, mink or voles.
Those prions — which Sim calls “shape-shifters” — are more likely to become diseased in the host animals, which then pose greater dangers to the health of humans who may eat those host animals, said Sim, whose research was published in the peer-reviewed Journal of Biological Chemistry.
“Something happens to that prion protein when you pass it through other animals, other hosts, and that’s what we call adaptation,” said Sim.
“That’s very important because for the current prion disease of concern in our society — chronic wasting disease, which is really spreading throughout the prairies — as far as we can tell … doesn’t seem to affect humans directly, but you pass it through some intermediate hosts, it can possibly adapt and that adapted form of the prion might then have a big effect on people.”
Humans, for instance, don’t seem to contract scrapie — another prion-related brainwasting and fatal disease — from sheep. But if a vole eats the feces of the sheep with the shape-shifting prion, it may be more prone to infection. If it then dies in an enclosed cow paddock, with its decomposing body becoming part of the soil and the grass which the cow then eats, Sim’s research suggests humans might be more at risk of contracting the disease from eating that cow. The cow is also more likely to become infected, especially since chronic wasting prions can stay in soil for up to two to three years, maybe even as long as five or 10, Sim said.
“It’s basically the implication of how (the prion) can adapt through the environment, through other animals that we may either eat, or what we eat will eat, because once you get these in the environment, it’s a complex food system. … In theory, it can certainly spread up the food chain and humans are at the top.”
While Sim said prion diseases don’t easily spread from one species to another one, she said slight differences in prion shapes make certain species more likely to either get infected or remain resistant. Horses and dogs, for instance, don’t get chronic wasting or mad cow disease.
“Reassuringly, it takes a lot of prions to cause the disease across the species barrier, but at the same time, we have to understand how this shapeshifting occurs if we’re going to have any hope of knowing what to look for, where to look and how to stop it,” Sim said.
She said more research is already being done to determine the exact shape of prions so that diagnosis doesn’t require a brain sample, and future treatment will better target it.
Currently, there is no treatment because the prions fold, clump together and become so solid no enzyme has yet to succeed in breaking it down, Sim said.
When prions clump together in humans with Creutzfeldt Jakob Disease, the prions eat holes into the brain, causing decreased movement and mental ability, leading to dementia and death.
Ron Clarkson, director of the prion program at the Alberta Prion Research Institute, said learning more about how the disease is spread is crucial in a province that relies on its cattle and elk industry.
“There are implications in the wild in terms of transmitting from deer to elk to possibly caribou,” said Clarkson, whose institute funds Sim’s research. “It covers vast regions and impacts the food source for our native groups.”
Cindy Lieu, a spokeswoman for the prion research institute, said one case of a local cow contracting mad cow disease in 2003 caused a $9-billion loss.
“We need to be on guard in terms of being proactive with this research,” Lieu said.