Prions more mobile than thought

The protein-based pathogens known as prions may pass between different species more easily than has been thought, a team of French researchers reports in the Jan. 27 Science. By infecting engineered mice with prions from cows and goats, scientists also have shown that the invaders readily target tissues other than the brain.

“We may underestimate the threat posed by some of these diseases by focusing only on the brain,” says Pierluigi Gambetti, a prion researcher at Case Western Reserve University in Cleveland. “It adds a new element to the equation.”

The research also raises the possibility that new prion strains recently identified in cattle and small rodents might be able to jump to other species, including humans.

“We should, in the future, be more exhaustive when looking at the possibility of prions being passed from one species to another,” says Hubert Laude, a professor at the French National Institute for Agricultural Research in Jouy-en-Josas and a coauthor of the study.

Prions closely resemble normal proteins made by a host. When prions invade a host, they propagate by forcing these normal host proteins, actually called prion proteins, to assemble improperly. When these malformed proteins accumulate in the brain, they cause mind-wasting conditions such as Creutzfeldt-Jakob disease in people and scrapie in sheep.

For the most part, intrinsic biological differences between species prevent these pathogens from jumping hosts. But some prions are known to be transmitted between species, including variant Creutzfeldt-Jakob disease, which humans contract after being exposed to mad cow disease in cattle.

“This barrier can be very, very strong or easily broken,” Laude says. “It depends on the species, the donor, host and also the strain of prion.”

To measure the strength of this barrier, Laude’s team used genetically engineered mice that expressed the normal human prion proteins. The scientists injected the mice with prions known to target similar proteins from cows or goats.

Laude’s team found misassembled proteins in the spleens of over half the mice, suggesting that this tissue might be more susceptible to infection. Malformed proteins were also detected in some of the animals’ brains, though the mice all lived out a normal life span and didn’t exhibit any signs of disease. 

Taken together, these findings suggest that prions once believed to be limited to only one species can jump the barrier and affect other species.