Principal Investigator/Program Director (Last, first, middle): Morales, Rodrigo ABSTRACT Chronic Wasting Disease (CWD) is a prion disease affecting several species of cervids. During the last years, CWD has acquired notoriety due to its high incidence on wild and captive animals. It is speculated that the number of animals afflicted by this disease will increase in the near future. Importantly, deer share their habitats with several other species, including humans. The potential of CWD prions to infect other animal species is still controversial. The leading event thought to cause the CWD epidemic involves the accumulation of infectious prions in environmental components. Prions have been shown to efficiently bind soil particles while maintaining their infectious properties. The elimination of prions from urine, feces and saliva from infected animals could be importantly participating in the spread of infectivity to the environment. We have recently shown that prions can bind living plants with great efficiency. Prion-contaminated leaves or roots infect experimental subjects with relatively short incubation periods. Interestingly, we have also shown that plants can uptake prions from soil and transport them to aerial parts. Preliminary data show that other natural and human-made surfaces can also bind and release prions in a material-specific manner. Importantly, prions bound to several materials can promote disease only by contact. Finally we have shown that earthworms can act as efficient disseminators of prion infectivity, either by attaching prions to their surfaces or by ingestion and further excretion of contaminated soil particles. In this project, we plan to further assess the binding properties of prions to soil, plants and earthworms. This will be achieved by using a wide variety of techniques (radiolabeling, qPMCA and bioassays). In parallel, samples obtained from CWD affected premises will be analyzed. We strongly believe that data obtained from these experiments will help us to understand the mechanisms of natural CWD spread and help to design new regulations and guidelines to eradicate the CWD agent from the environment.
Morales, Rodrigo PROJECT NARRATIVE Compelling evidence suggest that environmental prion contamination is the main responsible for the CWD epidemics affecting cervids. The persistent prion agent can get into the environment by decaying carcasses, or release of biological products such as urine, feces, saliva and placenta. Infectious prions bind soil particles without losing their biological properties. Results from our laboratory show that infectious prions can also bind to plant components and several other materials. Interestingly, we found that earthworms can facilitate the spread of the infectious agent by direct binding or by transport of contaminated soil particles. In this project we will assess whether cumulative prion contamination by excreta is able to be concentrated in soil and other surfaces while increasing their potential to infect nave animals. Binding properties will be assessed and quantified using different methods. Importantly, we will assess the potential of CWD infected plants designated for consumption to misfold the human version of the prion protein. As part of the experimental plan, we will standardize conditions to assess, in an effective and rapid way, the presence and amount of infectivity in premises suspected to carry CWD infectivity. Results from these experiments will complement our current view of the CWD epidemic and help to design efficient methods to eradicate it.
| Pritzkow, Sandra; Morales, Rodrigo; Lyon, Adam et al. (2018) Efficient prion disease transmission through common environmental materials. J Biol Chem 293:3363-3373 |
| Kramm, Carlos; Pritzkow, Sandra; Lyon, Adam et al. (2017) Detection of Prions in Blood of Cervids at the Asymptomatic Stage of Chronic Wasting Disease. Sci Rep 7:17241 |
| Morales, Rodrigo (2017) Prion strains in mammals: Different conformations leading to disease. PLoS Pathog 13:e1006323 |
