Oral transmission of prions is enhanced by binding to soil
Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases of sheep, deer, and elk. Transmissible spongiform encephalopathies (TSEs) are a group of incurable neurological diseases likely caused by a misfolded form of the prion protein. TSEs include scrapie in sheep, bovine spongiform encephalopathy (mad cow disease) in cattle, chronic wasting disease in deer and elk, and Creutzfeldt-Jakob disease in humans. Scrapie and chronic wasting disease are unique among TSEs because they can be transmitted between animals, and the disease agents appear to persist in environments previously inhabited by infected animals. Soil has been hypothesized to act as a reservoir of infectivity and to bind the infectious agent.
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 retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of montmorillonite and soil-bound prions. We establish that prions bound to montmorillonite are orally bioavailable, and that, unexpectedly, binding to montmorillonite significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Oral exposure to montmorillonite-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.
