Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles

PLoS Pathogens

Debbie McKenzie¹  Joel A Pedersen²  Judd M Aiken²  Rick J Chappell³  Christopher J Johnson⁴ 

[1] Biostatistics and Medical Informatics, University of Wisconsin Medical School, Madison, Wisconsin, United States of America;Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America;Department of Soil Science and Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America;Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America

关键词: Prion diseases;    Animal prion diseases;    Oral diseases;    Hamsters;    Sorption;    Oral administration;    Veterinary diseases;    Immunoblotting;   

DOI  :  10.1371/journal.ppat.0030093

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of Mte- and soil-bound prions. We establish that prions bound to Mte are orally bioavailable, and that, unexpectedly, binding to Mte significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Cox proportional hazards modeling revealed that across the doses of TSE agent tested, Mte increased the effective infectious titer by a factor of 680 relative to unbound agent. Oral exposure to Mte-associated prions led to TSE development in experimental animals even at doses too low to produce clinical symptoms in the absence of the mineral. We tested the oral infectivity of prions bound to three whole soils differing in texture, mineralogy, and organic carbon content and found soil-bound prions to be orally infectious. Two of the three soils increased oral transmission of disease, and the infectivity of agent bound to the third organic carbon-rich soil was equivalent to that of unbound agent. Enhanced transmissibility of soil-bound prions may explain the environmental spread of some TSEs despite the presumably low levels shed into the environment. Association of prions with inorganic microparticles represents a novel means by which their oral transmission is enhanced relative to unbound agent.

【 授权许可】

CC BY