Chronic wasting disease, or CWD, is a contagious and fatal prion disease that affects species of cervids such as deer, elk, caribou, reindeer and moose. Deer of all ages, captive and wild, can be affected.
The Centers for Disease Control and Prevention reports that CWD is prevalent in the continental United States, Canada, Norway, Finland, Sweden, and South Korea. The increased prevalence and spread of CWD endangers deer populations in these regions. No vaccine or treatment exists.
Prions are misfolded proteins capable of transmitting their misfolded form to normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals.
Like any prion disease, CWD is characterized by the misfolding of a normal protease-responsive host protein, or PrPC, into a protease-resistant isoform, or PrPSc. Misfolded pathogenic PrPSc has distinct biochemical profiles that correlate with specific disease features. CWD spreads when PrPSc is released into the environment through urine, feces, body fluids or carcasses or through direct animal-to-animal contact.
Mark Zabel leads a team at Colorado State University studying prion diseases.
“Chronic wasting disease can have serious consequences,” he said. “In Colorado and Wyoming, where the disease was first discovered, prevalence rates in specific herds are estimated to be between 30% and 50%. This rate of population decline can lead to local extinction of deer species.
Although CWD is a neurodegenerative disease, in deer PrPSc proteins are mainly of lymphogenic origin. Once PrPSc enters the body through oral or intranasal ingestion, it is replicated in the retropharyngeal lymph nodes, or LN. PrPSc eventually accumulates in the obex, a spinal region of the central nervous system, or CNS, leading to wasting and spongiform encephalopathy.
Typical of prion diseases, CWD is neurological and the CNS has the highest concentration of prions, so research has focused on brain-derived prions. However, infectious prions excreted in CWD mainly originate from the lymphoreticular system.
In a recent article from Journal of Biological ChemistryZabel’s team reports differences in the biochemical profiles of prion strains of lymphogenic and neurogenic origin in free-ranging white-tailed deer.
Zabel and his team report that paired obex and LN-derived prions from the same animal showed no significant difference in conformational stability, nor substantial inter-animal variation within the same tissue.
Glycoform ratio analysis showed differences in the glycosylation patterns of obex- and LN-derived prions in the same animal. To the team’s surprise, the LN-derived glycosylation patterns showed only marginal differences between the animals, but the brain-derived prions showed significant differences.
Using an ELISA-based structural profiling assay, the authors also observed greater conformational diversity in LN-derived prions than in brain-derived prions.
“The prions that exist in infected animals are usually not a singular species, but some kind of quasispecies or a cloud of different subspecies,” Zabel said. “We would say that the predominant species are selected inside the animal from a large pool of diverse prions.”
Based on their observations, the authors propose that the predominant neurogenic PrPSc isoforms are selected by the brain from a larger pool of LN-derived PrPSc. The neurogenic prion strains selected can vary widely from animal to animal.
Extraneural prion strains released into the environment may have a weaker species barrier than neurogenic prions. The ability to transmit infectious prions between species increases the zoonotic potential, or ability to infect humans, of CWD. The study highlights the importance of including strain properties alongside prion positivity as criteria for diagnostic tests used by wildlife management agencies.