The misfolded proteins responsible for a fatal neurological illness in deer exhibit a unique twist. Researchers have unveiled the first detailed structure of an infectious prion causing chronic wasting disease (CWD), which could aid in vaccine development or explain why the illness has not yet crossed over to humans. Published on October 24 in Acta Neuropathologica, the study highlights a 180-degree twist between two sections of the prion, a feature absent in rodent-adapted versions used for disease study.
Similar to Creutzfeldt-Jakob disease in humans, CWD prions in deer, elk, and moose transform a normal brain protein called PrP into misshapen versions that aggregate and lead to symptoms like listlessness, significant weight loss, and loss of fear. Although no human cases have been reported, and studies in mice and primates indicate a very low risk, the spread of CWD among animals consumed by humans raises concerns about potential transmission.
Understanding the misfolding of deer prions could shed light on why CWD does not easily infect humans. However, prions are notoriously difficult to study due to their sticky nature and tendency to clump together, making it challenging to obtain a clear image of diseased prions. Previous research on other prions, including those adapted from sheep and studied in rodents, showed that the proteins stack like plates.
Using hundreds of thousands of electron microscopy images, researchers discovered that a natural prion from white-tailed deer brain tissue stacks similarly but with notable differences, including the 180-degree twist. This twist, along with other convoluted loops in the deer prion, could either facilitate rapid spread among deer or hinder infection in humans.
The structural insights could help researchers hypothesize potential mechanisms preventing human infection, such as repulsive electric charges or fitting issues. Additionally, the structure could guide the development of vaccines or drugs that prevent prion aggregation, according to Byron Caughey, a biochemist at the National Institutes of Health’s Rocky Mountain Laboratories.
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