The misfolded proteins responsible for a fatal neurological disease 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 disease has not yet made the leap to humans, researchers report Oct. 24 in Acta Neuropathologica. One such feature is a 180-degree turn between the two sections of the prion. In the versions designed to infect rodents to study the disease, this twist does not exist.
Like the prion disease Creutzfeldt-Jakob disease in humans, CWD prions in deer, elk, and deer transform a healthy brain protein called PrP into misshapen versions that clump together and cause symptoms such as insomnia, drastic loss of weight and lack of fear.
While no humans have contracted the disease, and studies in mice and primates suggest the risk to humans is extremely low, the spread of CWD among animals that humans eat has raised concerns that it could one day spread to humans.SN: 6/10/24). Understanding how deer prions misfold may help unravel why CWD doesn’t spread easily 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 stick together,” it’s hard for researchers to get 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 clump together like plaques. Using hundreds of thousands of electron microscopy images, Caughey and colleagues discovered that a naturally occurring prion from the brain tissue of a white-tailed deer aggregates in a similar way, but with some potentially key differences.
The 180-degree twist in the protein is “the most dramatic change,” says Caughey. The rodent-adapted versions also have some loops that the deer prion lacks, or that “are all complicated by twists and turns” in the deer version.
Whether these differences enable the rapid spread of CWD among deer or make it difficult for deer prions to infect humans is unclear. But the structure can help researchers “at least make a tentative guess,” Caughey says. For example, it is possible that repulsive electrical charges or assembly problems may make it difficult for human PrP to aggregate into 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.
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