The misfolded proteins responsible for a fatal neurological illness in deer have a twist.
The first detailed structure of an infectious prion that causes chronic wasting disease, or CWD, reveals features that could help guide vaccine development or explain why the illness hasn’t yet made the leap to people, researchers report October 24 in Acta Neuropathologica. One such feature is a 180-degree twist between two sections of the prion. In versions engineered to infect rodents in order to study the disease, that twist doesn’t exist.
Like the prion illness Creutzfeldt-Jakob disease in people, CWD prions in deer, elk and moose transform a healthy brain protein called PrP into misshapen versions that clump together and cause symptoms such as listlessness, drastic weight loss and lack of fear.
While no person has contracted the disease and studies in mice and primates suggest that the risk to humans is extremely low, CWD’s spread among animals that people eat has raised concerns that it one day could jump to people (SN: 6/10/24). Understanding how deer prions misfold could help reveal why CWD doesn’t easily spread to humans.
But “prions are messy,” says Byron Caughey, a biochemist at the National Institutes of Health’s Rocky Mountain Laboratories in Hamilton, Mont. Because the proteins “are very sticky and they tend to cling together,” researchers have a tough time getting a clear picture of what diseased prions look like.
Previous studies looking at other prions, including rodent-adapted versions originally from sheep, showed that the proteins stack together like plates. Using hundreds of thousands of electron microscopy images, Caughey and colleagues found that a natural prion from the brain tissue of a white-tailed deer stacks in a similar way, but with some potentially key differences.
The 180-degree twist in the protein is the “most dramatic difference,” Caughey says. Rodent-adapted versions also have some loops that the deer prion lacks, or that “are all convoluted by the twists and turns” in the deer version.
Whether these differences enable CWD’s rapid spread among deer or make it difficult for deer prions to infect people is unclear. But the structure can help researchers “at least preliminarily guess,” Caughey says. For instance, it’s possible that repulsive electric charges or problems fitting together could make it hard for human PrP to stack onto the CWD prion.
Having the structure could also help scientists develop vaccines or drugs that prevent prion clumps from forming in the first place, Caughey says.
