Abstract
Ingestion of prion-contaminated materials is postulated to be a primary route of prion disease transmission. Binding of prions to soil (micro)particles dramatically enhances peroral disease transmission relative to unbound prions, and it was hypothesized that micrometer-sized particles present in other consumed materials may affect prion disease transmission via the oral route of exposure. Small, insoluble particles are present in many substances, including soil, human foods, pharmaceuticals, and animal feeds. It is known that meat and bone meal (MBM), a feed additive believed responsible for the spread of bovine spongiform encephalopathy (BSE), contains particles smaller than 20 μm and that the pathogenic prion protein binds to MBM. The potentiation of disease transmission via the oral route by exposure to MBM or three micrometer-sized mineral feed additives was determined. Data showed that when the disease agent was bound to any of the tested materials, the penetrance of disease was increased compared to unbound prions. Our data suggest that in feed or other prion-contaminated substances consumed by animals or, potentially, humans, the addition of MBM or the presence of microparticles could heighten risks of prion disease acquisition.
Acknowledgments
We thank Dr. Carl Parsons (University of Illinois, Urbana-Champaign) for the generous gift of MBM, Dr. Richard Rubenstein (SUNY Downstate Medical Center) for the gift of the 3F4 monoclonal antibody, Kartik Kumar for bibliographic assistance, and Drs. Julia Rodriguez-Ramos and Diego Calderon for their comments on the article. This work was supported in part by grants from the U.S. Department of Defense (DAMD17-03-1–0369) and National Institutes of Health (1R01 NS600341). Any use of trade, product, or firm names is for descriptive purposes only and does not imply endorsement by the U.S. government.