Prions and Prion-like Proteins
Note: This information applies to prion work requiring BSL2 containment or BSL2 enhanced only. If your work with prions requires BSL3 containment (e.g. Creutzfeldt-Jacob disease, Kuru agents), a separate risk assessment must be performed in consultation with the BSL3 Program and the Biosafety Officer.
All prions, whether of human or animal origin, are subject to IBC oversight as infectious agents. All wild-type and mutant Prion-like Proteins (PLPs) that have a human genetic origin are subject to IBC oversight except the few cases in which the disease is entirely genetic (e.g. polyQ disorders). Approved protocols are effective for three years with annual review.
Note: Animal PLPs are generally excluded from IBC oversight unless significant functional homology exists between the animal PLP and human ortholog that could reasonably cause concern for human health (e.g. an animal PLP showing cross-seeding/transmissibility potential with a human PLP).
A United States Department of Agriculture (USDA) import permit is required to receive and work with animal prions (which includes cross state lines). Visit USDA Permits and Certifications for more information.
Definition of Prions and PLPs
Prions are defined as:
- Altered conformations of PrP that cause Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt Jakob Disease (vCJD), kuru, fatal familial insomnia, Gerstmann-Straussler-Scheinker syndrome, Huntington Disease-like 1, bovine spongiform encephalopathy, feline spongiform encephalopathy, transmissible mink encephalopathy, scrapie (sheep), chronic wasting disease (deer, moose, reindeer, red deer, mule deer, sika deer).
- Possibly, altered conformations of the alpha-synuclein protein that cause multiple systems atrophy.
- Proteins that confer a disease state that is transmissible from cell to cell.
PLPs are defined as:1
- Fragments of amyloid fibrils formed from alpha-synuclein protein (Parkinson’s disease); tau protein (tauopathies); beta-amyloid protein (Alzheimer’s disease); RNA-binding protein fused in sarcoma (FUS) (frontotemporal lobar dementias, amyotrophic lateral sclerosis); polyglutamine containing proteins (polyQ) (Huntington’s disease, some ataxias); superoxide dismutase 1 (amyotrophic lateral sclerosis); transactivation response element (TAR) DNA-binding protein-43 (TDP-43) (amyotrophic lateral sclerosis, hippocampal sclerosis, limbic-predominant age-related TDP-43 encephalopathy); ubiquilin (amyotrophic lateral sclerosis).
- Fragments of amyloid fibrils that have been shown to “seed” a pathology, cause a disease, or both.
Risk Factors When Working With Prions and PLPs
A risk assessment must be performed for work involving prions and PLPs. There are no known effective treatments or vaccines for prion diseases (also known as Transmissible Spongiform Encephalopathies or TSEs). It is necessary to handle prions and PLPs with extreme caution, both for worker protection and for environmental protection. The highest concentrations of prions in infected animals are in the central nervous system and its coverings. Based on animal studies, it is likely that prions are also found in the spleen, thymus, lymph nodes, skin, blood, and intestine.
Prions are highly resistant to conventional inactivation procedures (heat and chemicals). In contrast, PLPs are generally inactivated using conventional procedures (heat and chemicals). Prions are transmissible by inoculation, ingestion, or transplantation of infected tissues or homogenates, while transmissibility of PLPs has been demonstrated only in limited experimental conditions with a few PLPs. Nevertheless, out of an abundance of caution, the following factors related to Prions or PLPs must be considered when conducting a risk assessment:
- Quantities and concentrations (e.g., purified misfolded Prions or PLPs)
- Transmissibility potential
- PLP disease-causing potential
- Disease tissue type and potential infectivity (e.g., diseased CNS homogenate)
- Resistance to decontamination
- Environmental stability
- Aerosol generation (e.g., sonication of fibrils or tissues containing fibrils in homogenates of diseased tissue, etc.)
- Use of sharps (e.g., direct brain injections)
 See Prion-Like Proteins in Phase Separation and Their Link to Disease for introduction of Prion-like Proteins.