Re: how are prions transmitted through intestinal barrier?

Hi Derrick,

Thanks for this interesting question. It's true that if as is believed, prions are transmitted through ingestion, they must be able to survive the digestive processes in the stomach and the small intestine. As you probably know there are 2 structural forms of prions. Normal prion is found in the nervous tissue of animals and has a homologue in yeast. Its function is unclear; you can knock out the prion gene in mice with apparently no effect. The infectious, or active form of prion protein has a different structure and it is highly resistant to treatments that normally denature proteins, such as heating, acid and organic solvents. It is also very resistant to protease digestion with enzymes like trypsin or chymotrypsin, in fact this is how it was first distinguished. So it seems likely that this form of prion could survive the pH and enzymes of the stomach and the gut.

How prion gets from the gut to the nervous system is an interesting question. The digestive system has an extensive and complex nervous system of its own, which is part of the peripheral nervous system. It's thought that prions can be absorbed at areas called Peyers patches, where areas of lymphoid tissue contact the gut. These areas are normally involved in taking up microorganisms and presenting them to the immune system. Prions could be taken up into lymphoid cells, then transported around the lymph system to places like the spleen, tonsils or lymph nodes. Here, they would convert normal prion in the contacting nervous tissue to infectious prion and this process could eventually travel along nerves to the central nervous system and the brain. This process has been observed to some extent in mice and people have suggested the tonsils as a good place to look for prions during the long incubation period before the disease shows.

However, bear in mind there is still a lot of controversy in this area. For instance, it's still not certain that humans contracted CJD from BSE by this route-though the evidence (the prions involved are immunologically identical) is strong. And there are still those who believe that there may be a tiny nucleic acid component to prions, as yet undetected.

For further reading, I recommend the book "Deadly Feasts" by Richard Rhodes. On the web, the very best source of information is The Official Mad Cow Disease Home Page at http://www.mad-cow.org, which has all the latest research news. There is also good science information at http://www.t ulane.edu/~dmsander/WWW/335/Prions.html

Neil Saunders