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Updated: Jun 27, 2026
Protein Misfolding Cyclic Amplification of Prions
Published on: November 7, 2012
Prion interference with multiple prion isolates
Charles R Schutt1, Jason C Bartz
1Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska 68178, USA.
Abstract:
Co-inoculation of prion strains into the same host can result in interference, where replication of one strain hinders the ability of another strain to cause disease. The drowsy (DY) strain of hamster-adapted transmissible mink encephalopathy (TME) extends the incubation period or completely blocks the hyper (HY) strain of TME following intracerebral, intraperitoneal or sciatic nerve routes of inoculation. However, it is not known if the interfering effect of the DY TME agent is exclusive to the HY TME agent by these experimental routes of infection. To address this issue, we show that the DY TME agent can block hamster-adapted chronic wasting disease (HaCWD) and the 263K scrapie agent from causing disease following sciatic nerve inoculation. Additionally, per os inoculation of DY TME agent slightly extends the incubation period of per os superinfected HY TME agent. These studies suggest that prion strain interference can occur by a natural route of infection and may be a more generalized phenomenon of prion strains.
Insights
The drowsy (DY) transmissible mink encephalopathy (TME) agent blocks other prion strains, including hamster-adapted chronic wasting disease (HaCWD) and scrapie, from causing disease. This prion strain interference may occur naturally and is a widespread phenomenon.
Area of Science:
- Neuroscience
- Infectious Diseases
- Veterinary Medicine
Background:
- Prion diseases are fatal neurodegenerative disorders caused by misfolded prion proteins.
- Prion strain interference describes how one prion strain can inhibit another's replication or disease-causing ability.
- The drowsy (DY) strain of transmissible mink encephalopathy (TME) is known to interfere with the hyper (HY) TME strain.
Purpose of the Study:
- To investigate if the interfering effect of the DY TME agent extends beyond the HY TME strain.
- To determine if DY TME agent interference occurs via natural routes of infection, such as sciatic nerve or oral inoculation.
- To assess the broader applicability of prion strain interference.
Main Methods:
- Hamsters were intracerebrally, intraperitoneally, or via sciatic nerve inoculated with DY TME agent alone or in combination with HY TME, hamster-adapted chronic wasting disease (HaCWD), or 263K scrapie agents.
- Per os (oral) inoculation was used to assess interference between DY TME and HY TME agents.
- Incubation periods and disease progression were monitored to evaluate the interfering effects.
Main Results:
- DY TME agent blocked disease caused by HaCWD and 263K scrapie agents following sciatic nerve inoculation.
- DY TME agent also extended the incubation period of HY TME agent when co-inoculated per os.
- These findings demonstrate that DY TME agent interference is not limited to the HY TME strain and can occur via natural infection routes.
Conclusions:
- Prion strain interference is a more generalized phenomenon than previously thought.
- The DY TME agent can interfere with a broader range of prion strains and infection routes.
- Prion strain interference may play a significant role in the natural transmission and pathogenesis of prion diseases.
