What makes prions so deadly
How dangerous are scrapie prions?
So far, only BSE prions were considered to be transmissible to humans. But in mice, scrapie prions can also turn human proteins into disease-causing variants.
Stephanie Lahrtz ⋅ Twisted, disease-causing prion proteins can arise in many mammals from naturally occurring, healthy prions. Twisted prions have the potential to cause fatal brain degeneration, such as Creutzfeldt-Jakob disease (CJD) in humans, BSE in cattle or scrapie in sheep. Scrapie prions are considered harmless to humans, in contrast to BSE prions. If the latter get into the human organism, they stimulate healthy prions there to twist. This can lead to a fatal disease similar to CJD called vCJD. But now a study suggests that scrapie prions could also be less harmless than assumed.1
An international team led by Olivier Andreoletti from the University of Toulouse has injected scrapie prions of various twisted shapes directly into the brain of mice. These mice carried the gene for the human prion protein, so they had the human proteins in their cells. This procedure is considered a standard experiment and currently the best model for testing the transferability and infectivity of prions.
Contrary to the researchers' expectations, some of the test animals developed prion disease after the injection. The results of several biochemical analyzes of the disease-causing prions were even more surprising. The human twisted prions that had formed in the brains of the mice after the injection of the scrapie prions did not resemble the animal pathogens. Rather, they exhibited the characteristics of those prions found in the brains of patients with CJD. This means that human prions, at least in mice, can be stimulated to twist by scrapie prions, explains prion expert Adriano Aguzzi from the University of Zurich. That is completely new and unexpected.
Never before has scrapie in people
But that is not yet proof that scrapie prions are also infectious for humans, explains the expert. Aguzzi and the authors of the work still do not consider the scrapie prions to be dangerous. Because the disease scrapie has appeared in flocks of sheep for at least 250 years. But since then there have never been more than one or two cases of CJD per million people in any affected country. If scrapie prions were really deadly, then at some point there should have been a larger number of CJD patients, at least locally. So far, at least, that has not been noticed.
¹ Nature Communications, online publication December 16, 2014.
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