Persistent Prions: Soilbound Agents are More Potent!

Science News, July 21, 2007; Vol. 172, No. 3 , p. 36

Carolyn Barry

Deformed proteins called prions cause fatal brain-destroying disorders, such as chronic wasting disease in deer and elk and mad cow disease, which can infect people. Evidence suggests that prions make their way into animals’ nervous systems through ingestion, but scientists aren’t sure.

A new study shows that prions become more infectious when they latch on to soil particles that animals eat, suggesting that ingestion is a primary route of disease transmission. “Our study points us in one direction that explains how these animals are getting infected,” says study author Judd Aiken of the University of Wisconsin–Madison.

Prions enter the environment from the remains of infected animals, and, to some degree, from body fluids such as urine and saliva. Prions linger in soil for at least 3 years (see related SN article below) by binding tightly to clay and other minerals. Aiken had hypothesized that soil would hinder the action of the clingy prions, making them less infectious. He was surprised to find the opposite.

“The binding of infectious agents in soil actually greatly enhances the infection,” Aiken says. “It makes the disease more transmissible.”

Wild and farm animals often swallow up to several hundred grams of soil per day when eating plants, drinking muddied water, and licking the ground to get minerals. In doing so, they may consume prions. The relationship between ingestion and infectivity is unclear, though, because previous experiments showed that prions are inefficient at infecting animals that eat diseased tissue.

Aiken and his team fed each of three groups of hamsters a different soil type containing prions. Other hamsters were given an equivalent dose of a prion mixture derived from the brains of infected animals. All soil-eating hamsters were at least as likely to contract the prion disease as those that had ingested the prion-brain mixture, which has been considered an efficient transmitter of prions.

Two of the three soils had an even more dramatic effect. Hamsters that ate either of those soils had a higher rate of prion disease than did animals that ate the prion-brain mix. Animals that ate the third soil, which contained more organic matter than the other two did, had the same infection rate as hamsters that ate the prion-brain mix.

Researchers hypothesize that soil might protect prions from the destructive environment of the digestive system. Alternatively, Aiken says, soil particles might break up clumps of prions into smaller, more numerous clusters. Or, the particles could change the way in which prions enter nervous system tissues.

The study, in the July PLoS Pathogens, yielded “very fascinating findings,” says Michael Miller, a wildlife veterinarian at the Colorado Division of Wildlife in Fort Collins. “It ties together observations that people have made throughout the years.” He suggests that the different infectivity rates of prions in the three soils may also explain why the disease afflicts animals in some areas more than in others.

Prions’ Dirty Little Secret

Science News, Feb. 11, 2006; Vol. 169, No. 6 , p. 93

Janet Raloff

Fifteen years ago, scientists at the National Institutes of Health reported that malformed prions—proteins that can trigger lethal illnesses including mad cow disease—remain on soil surfaces for at least 3 years. Now, scientists report why rain doesn’t flush away the prions: The proteins bind almost irreversibly to clay.

In fact, clay can “retain up to its own mass of … prion proteins,” says Peggy Rigou of the National Institute of Agronomic Research (INRA) in Jouy-en-Josas, France.

Her team added sheep prions to pure clay, sandy soil, and loam. Positively charged parts of the protein molecules bound to the negatively charged surface of the clay that was present in all the soil samples. Extensive washing failed to dislodge the prions. However, when the chemists treated the mixtures to make the proteins negatively charged and then ran an electric current through each mixture, the prions migrated off the clay particles.

Freeing the prions was a major achievement, Rigou notes, because it enables scientists for the first time to measure prion concentrations in soil. Until now, no technique could confirm that intact prions were present in soil. In an upcoming Environmental Science & Technology, her team reports that the new procedure permits detection of concentrations as low as 0.2 part per billion.

Soils might acquire prions from animal wastes or carcasses. Scientists’ concern is that livestock might ingest infected clay particles while eating grass or drinking from mud puddles, Rigou says.

PRION is an acronym for a unique infectious agent called a prion (proteinaceous infectious particle), composed of abnormal proteinaceous material devoid of detectable amounts of nucleic acid. These are abnormal versions of prion protein, or “PrP” which is ubiquitous to cell membranes, but is highly species specific. These infective agents can infect cows in the form of Bovine Spongiform Encephalopathy (BSE) and is also known as “Mad Cows Disease”. Feline Spongiform Encephalopathy (FSE) occurs in cats. In sheep and goats, the disease is called Scrapie, In mink, the disease is Transmissible Mink encephalopathy (TME). In mule deer and elk, the disease is called Chronic Wasting disease. Human disease can be classified as Creutzfeldt-Jakob Disease (CJD), variant CJD (vCJD), Gerstmann-Staussler-Scheinker Disease (GSS), Kuru, Fatal Familial Insomnia (FFI), or in infants, Alpers Syndrome.

Virulence Factors: Prions are proteins. The body encodes a gene for a normal protein, PrP, usually found in lymphocytes and CNS neurons. PrP has a normal conformation known as PrPc, which is genetically encoded. It becomes misfolded into a form known as PrPsc, and causes other proteins to become misfolded as well.

The protein goes from a 40% alpha helix with almost no beta sheet to 30% alpha helix and 45% beta sheet but retains same amino acid sequence. It had previously been thought that the amino acid sequence could have mainly one active structure, but this shows that’s not true. Unlike PrPc, the misfolded PrPsc is not easily digested by proteases. It does not cause an immune response. The abnormal protein can’t be broken down in the body and so it aggregates in the brain.

These particles do not infect cells or tissues and propagate, but rather are able to convert normal prion proteins into the abnormal form. The conversion rate is logarithmic but slow.