Aerosols transmit prions to immunocompetent and immunodeficient mice
Johannes Haybaeck1, Mathias Heikenwalder, Britta Klevenz
1Department of Pathology, Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
Abstract:
Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrP(C), efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrP(C) selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrP(Sc) and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.
Insights
Airborne prions efficiently cause scrapie in mice through inhalation, directly invading neural pathways. This finding suggests a previously unrecognized risk of prion transmission via aerosols, necessitating updated biosafety protocols in laboratories.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biochemistry
Background:
- Prions cause transmissible spongiform encephalopathies (TSEs) and are known to infect hosts via oral, parenteral, intralingual, or transdermal routes.
- Airborne transmission of prions has not been previously considered a significant risk.
Purpose of the Study:
- To investigate the susceptibility of mice to aerosolized prions.
- To determine if airborne prions can cause disease without replication in lymphoid organs.
Main Methods:
- Exposure of various mouse models (wild-type, tga20, NSE-PrP transgenic) to aerosolized prions.
- Assessment of disease development and prion (PrPSc) presence in the brain.
- Inoculation of healthy mice with brain homogenates from diseased mice to confirm infectivity.
- Testing susceptibility in immunodeficient mouse models.
Main Results:
- Mice efficiently developed scrapie following exposure to aerosolized prions.
- Aerogenic infection occurred even in mice lacking key immune components.
- Diseased mice brains contained infectious PrPSc, confirming transmission.
- Prion disease developed without an obligatory replicative phase in lymphoid organs.
Conclusions:
- Aerogenic exposure to prions is a highly effective route of infection.
- Airborne prions can directly invade neural pathways.
- This study highlights a significant, previously underestimated risk of airborne prion transmission.
- Current prion biosafety guidelines may require re-evaluation in research and diagnostic settings.
