Autoclaving Prions

Human Prion Protein

One generally thinks of prions in the Scrapie form (PrPSc) as an infectious particle that is made up of protein that is abnormally folded. There are normally folded prions which are found in many organisms. This abnormally folded prion is the central ideal of the Prion Hypothesis, which is still controversial. Researchers generally think of infectious agents as being viral, bacterial, fungal or parasitic in nature which contain nucleic acids (i.e. DNA, RNA or both).

The word prion is derived from the words protein and infection. These infectious proteins cause transmissible spongiform encephalopathies in a number of mammals. These diseases include bovine spongiform encephalopathy (BSE) also known as mad cow disease in cattle. In humans the disease is known as Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD), Gerstmann-Straussler-Scheinker syndromeFatal Familial Insomnia and Kuru. All these diseases affect the structure of the brain generating fluid filled spaces referred to as spongiform. These diseases are currently untreatable and are fatal.

Abnormal prions propagate by transmitting a misfolded protein state. When a prion enters the body, it induces existing properly folded prions to convert into the abnormal conformation. The abnormal prion acts as a template to guide misfolding. The newly formed abnormal prions can then go and convert more normal prions into abnormal conformations. This generates a chain reaction that produces large quantities of abnormally folded prions. The propagation of prions requires the presence of normal prions. Animals that do not express normal prions do not get this disease nor can they transmit it.

All the known abnormal prions induce an amyloid fold which causes the normal protein to polymerize into an aggregate consisting of tightly packed beta sheets. These amyloid aggregates are fibrils that have the ability to grow at their ends and replicating when breakage causes two growing ends to become four growing ends. The incubation period for prion disease to develop is determined by the exponential growth rate associated with prion replication. A prion infection may lay dormant for years, however, when symptoms appear, death ensues within a few months.

This newly altered normal prion structure is stable and begins to accumulate causing massive tissue damage and cell death. This abnormally folded prion is resistant to denaturation by physical and chemical agents making destruction of this particle very difficult. There are a number of different prions, all having slightly different structure. During the replication process, prions are subjected to epimutations followed by natural selection like any other forms of replication. The precise structure of the prion is still not known nor is the mechanism of infection.

Although the Prion Hypothesis received the Nobel Prize, it is not certain that the infectious agent behind diseases such as scrapie or Creutzfeldt-Jakob disease is the so called “rogue” prion protein. Information provided by the SC GUT project, funded for five years via the European Commission’s Fifth Framework Programme, suggests something otherwise.

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As it turns out, scrapie (in sheep) is a considerable problem throughout most of the world and is the most widespread transmissible spongiform encephalitis (TSE) in Europe. It is believed that scrapie is the source of the BSE epidemic. Because of this, control and eradication of TSE in small ruminants is top priority in the European Union (EU).

Although abnormally folded prion proteins are characteristic of TSE, it may be possible that they are not the initial infectious agent. This idea is based on how prions are absorbed in sheep intestine. SC GUT researchers inoculated sheep intestines with brain extracts that contained abnormally folded prions believed to be the cause of TSE. They reported that the inoculated abnormal prions were detected for a short time (3.5 hours) in the wall of the gut and not in sites where disease generated prion protein aggregated. Normal prion proteins that became abnormally folded accumulated one month after inoculation and appeared at sites different from those sites where the inoculated abnormal prions were observed to be absorbed. Furthermore, experiments suggest that in normal animals, all the ingested prions would be digested before they could be absorbed by the gut. This suggests that prions do not cause disease by passing through the gut wall.

This finding doesn’t rule out the possibility that prions might still cause disease if absorbed in sufficient amounts but it is possible that prions may be able to directly infect nerve endings by some unknown mechanism. Nevertheless, research continues.

Sterilization of Prions

Prions are obviously different from other infectious agents in that they are infectious by their ability to cause conformational changes to normal prions. Hence, sterilizing prions requires denaturation of the protein to a state where the prion can no longer induce abnormal folding of normal prionsPrions have been demonstrated to be resistant to proteases, heat, radiation and formalin. Destruction of prions requires hydrolysis or reduction or destruction of tertiary structure. Keep in mind that partially denatured prions can be renatured into infectious particles under certain conditions.

Prions can be deactivated in a steam autoclave using a temperature of 270 °F (132 °C) at 21 psi for 90 minutes. If the prion infected material is in a solution of sodium hydroxide, steam autoclave at 250 °F ( 121 °C) at 21 psi for one hour.

A commercial disinfectant can also be used such as Environ LpH. Make a 1 percent solution and soak for 10 hours or you can use a 10 percent solution for one hour.

Prion Image Information

Picture description, url and author/attributions

Description: Human prion protein, residues 125-228, created from protein database (PDB) entry 1QM3. The coloring illustrates the subdomains, that are proposed to initiate the conversion from the normal cellular to the scrapie form by slow motions. Red: beta1-helix1-beta2. Blue: helix2-helix3 (picture created with PovRay). For scientific details see: S.Schwarzinger, A.H.C.Horn, J.Ziegler, H.Sticht J. Biomol. Struct. Dyn. 200623, 581-590.

Date: March 25, 2006

Source: Own work

Author: Cornu (talk) 19:04, 5 June 2009 (UTC)

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Further Reading:


Li J, Browning S, Mahal SP, Oelschlegel AM, Weissmann C (2010). “Darwinian evolution of prions in cell culture”Science 327 (5967): 869–72. Bibcode:2010Sci…327..869L. doi:10.1126/science.1183218. PMC 2848070. PMID 20044542. Lay summary.

Brown P, Rau EH, Johnson BK, Bacote AE, Gibbs CJ, Gajdusek DC (2000). “New studies on the heat resistance of hamster-adapted scrapie agent: threshold survival after ashing at 600 degrees C suggests an inorganic template of replication”Proceedings of the National Academy of Sciences of the United States of America 97 (7): 3418–21. Bibcode:2000PNAS…97.3418B. doi:10.1073/pnas.050566797. PMC 16254. PMID 10716712.

“Ozone Sterilization”. UK Health Protection Agency. 2005-04-14. Archived from the original on 2008-05-22. Retrieved 2010-02-28.

Brown, P. (2003). “Ultra-high-pressure inactivation of prion infectivity in processed meat: A practical method to prevent human infection”. Proceedings of the National Academy of Sciences 100 (10): 6093–6097. doi:10.1073/pnas.1031826100.

Johnson, Christopher; Bennett; Biro; Duque-Velasquez; Rodriguez; Bessen; Rocke; Bartz; James P. Bennett, Steven M. Biro, Juan Camilo Duque-Velasquez, Cynthia M. Rodriguez, Richard A. Bessen, Tonie E. Rocke (17th). “Degradation of the Disease-Associated Prion Protein by a Serine Protease from Lichens”. In Bartz, Jason C. PLoS ONE 6 (5): 9836. Bibcode:2011PLoSO…6E9836J. doi:10.1371/journal.pone.0019836.

The [Het-s] Prion, an Amyloid Fold as a Cell Death Activation Trigger

Cellular mechanisms of prion propagation

QLK5-CT-2001-02332, SC-GUT,



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