Prion Proteins Might Not Cause Creutzfeld-Jacob

A new study indicates that abnormal prion proteins (PrP) might not be the infectious agent for variant Creutzfeld-Jacob disease (vCJD).

Since the first outbreak of bovine spongiform encephalopathy (BSE) in cattle and vCJD in humans, researchers have tried to understand how an abnormal variation of a normal protein can trigger an infectious disease.

Individual people and animals have different levels of genetic susceptibility to the disease. In a study published in the March 2006 Journal of Pathology, researchers investigated the transportation of prion protein across the intestinal mucosa of scrapie-sensitive and scrapie-resistant sheep. Scrapie is the sheep form of the disease. They found that when they injected abnormal PrP into the sheep's gut it was equally absorbed by all sheep. They concluded that the resistance was not achieved by blocking uptake of the abnormal proteins.

The researchers loaded a small area of the sheep's gut with a fluid mixture containing 0.5g of scrapie-infected brain containing a large amount of the disease-specific variant of the PrP. The abnormal PrP was taken up by villi but not by the Peyer's patches that are believed to be the places where animals amplify the infectious agent.

A mixture of disease-specific PrP predigested with standard stomach contents was injected into the gut, but no PrP was transferred to the villi. Western Blot analysis of the mixture showed that only a very small amount of the PrP had survived. Lead author Martin Jeffrey, Ph.D., of the Veterinary Laboratories Agency (Lasswade, UK), observed, "As sheep become infected, the theoretical probability that this is due to an invisible sub-fraction of digestion-resistant PrP molecules is unlikely.” He questions whether PrP is really infectious or whether it is really just a secondary marker indicating the presence of the scrapie agent.

Dr. Jeffrey said that if the infection were acquired from the mouth, the first tissues to accumulate infectivity would be the lymph nodes in the throat or the tonsils. This is not seen in animals and there is no reason to believe it would be so in humans.



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Veterinary Laboratories Agency