Prion diseases adapt, spread

LINDELL BEACH, B.C. — Research at the University of Alberta is shedding light on the complexity of prion diseases.

Researchers have discovered that these diseases can adapt to spread to other animals and other species.

A prion is an infectious agent in the form of a misfolded protein. All known prion diseases affect the structure of the brain and neural tissue, causing neurodegenerative conditions that are untreatable and fatal.

Prions are responsible for BSE in cattle, scrapie in sheep, chronic wasting disease in deer and variant Creutzfeldt-Jakob disease in humans.

They enter a healthy body either from being ingested or from the transfer of contaminated blood or blood products.

Once there, they can invade a normal host protein and fold it into an abnormal shape associated with disease. Acting as a template, it can then influence other normal proteins to fold abnormally.

This altered, folded structure is stable and causes tissue damage and cell death as the misfolded proteins accumulate. They can exist for years undetected by the immune system, manipulating their damage in the form of spongelike holes in nerve cells or brain tissue.

They have no need to metabolize and no capacity to reproduce.

According to the latest research, they adapt and replicate by making tiny changes to their makeup to move to other host animals.

“The type of change we saw is one that occurs naturally,” said neurologist Valerie Sim with the neurology division of the U of A’s Department of Medicine.

“It is basically different variations of the protein, coded for by our genetic makeup.… Every mammal that can get a prion disease has its own normal version of the prion protein. Each species has small prion protein differences, but even within a given species, there can be even smaller differences that affect the susceptibility of (individual) animals getting prion disease or what type of prion disease it gets.”

Prions can cross species barriers, but they must also overcome challenges because of the bigger differences between the prion proteins in one species compared to another, said Sim, whose research was published in the Journal of Biological Chemistry.

However, a species could be more susceptible to prion strains invading from other species if there are certain smaller variations of the prion protein within that species.

This holds true for individual animals as well, making some animals more susceptible than others. Prions must adapt to successfully invade another species, creating a new version of the disease in the process, but they remain strongly stable once established in the new host.

“This is because we don’t think it is evolving within a given species per se,” said Sim.

Once it is in a certain species, it remains relatively constant.

“It is more the transfer through species that is the concern, with adaptation occurring through each host. If we understand the nature of the disease in a given host, though, we have a relatively constant target at which to aim treatments.”

The discovery that prions can adapt and spread is of great concern to scientists because it opens up all kinds of worrisome scenarios. If a deer with chronic wasting disease is killed by a predator in the wild, could the prion cross into the new host, adapt and spread infection into a species not normally associated with a neurodegenerative disease?

“We know for some forms of prion disease (such as scrapie), the infectivity can remain in the soil for at least 16 years,” said Sim.

“It means there are tracts of land contaminated by prions, some of which may have these different variations which could, if our theory holds, make them more able to infect other animals. Anywhere infected deer have been, they are likely to leave behind prions.”

The prion protein is relatively recent in evolutionary terms.

Sim said scrapie in sheep has been around for centuries and was first reported in 1730, but the human neurodegenerative disease was only discovered in 1920.

However, researchers didn’t make the connection that these were infectious protein diseases until the mid-1960s through to the 1980s.

The human disease is sporadic in 90 percent of cases, which means it is not associated with exposure to outside prions. However, the catastrophic outbreak of BSE was due to the practice of feeding animal protein back to cattle, some of which could have been contaminated with sheep scrapie.

Sim also said the spread to humans could possibly have been from a rare case of sporadic BSE.

“There is strong evidence that vCJD came from mad cow disease through the food system,” she said.

“(The) brain and spinal cord had the most contamination, so any food preparations that were high in those components were the riskiest food items. There can be contamination in the nerves, which could be in preparations of (beef) muscle.”

Research continues into the adaptability and potential spread.

“So far, we discovered this adaptation tendency in the test tube using non-infectious prion protein, so now we are starting to look at actual infectious prions to see if some strains of prion disease are more prone to adaptation through these subtle changes in host prion protein,” said Sim. “In addition, we were using models of mouse prion disease, and we are now ex-panding to look specifically at the situation of chronic wasting disease.”

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