Novel prion strain causes chronic wasting disease in a Finland moose

By Dr. Priyom Bose, Ph.D.Reviewed by Benedette Cuffari, M.Sc.Jan 19 2023

Prions are proteins that cause fatal and incurable neurodegenerative diseases in humans and animals, some of which include sheep scrapie, chronic wasting disease (CWD) of cervids, Creutzfeldt-Jakob disease (CJD), and bovine spongiform encephalopathy. The continual emergence of novel prion diseases and strain variants has been reported, which has led to an increasing number of animal infections. Recently, CWD has raised concerns in the scientific community due to its uncontrolled contagious transmission.

Study: Novel Prion Strain as Cause of Chronic Wasting Disease in a Moose, Finland. Image Credit: ArtBBNV / Shutterstock.com

Structure and function of prions

Diseases caused by prions are highly contagious and spread through the infected animal's saliva, urine, blood, or feces. These diseases' exceptional transmissibility stems from the dynamic conformational properties of the prion protein (PrP).

The secondary structure of host-encoded cellular PrP (PrP^C) is α-helical. However, during disease, its moderately underglycosylated infectious counterpart (PrP^Sc) assembles into amyloid fibrils with parallel and intermolecular β-sheets. The replicative property of prions is based on the capacity of PrP^Sc to repeatedly template its conformation on PrP^C, which leads to an exponential accumulation of prions.

Although prions lack nucleic acids, they exhibit heritable strain properties that influence disease outcomes. This property affects patterns of neuronal degeneration, clinical signs, incubation period, defined as the time between infection and manifestation of symptoms, and PrP^Sc deposition in the central nervous system (CNS). The heritable property also influences the capacity of prions to replicate in non-CNS tissues, such as those within the lymphoreticular system.

The differential strain properties of prion species influence their capacity to cause disease. It has been observed that heritable strain information of prions is enciphered by distinct PrP^Sc conformations that are propagated during replication.

CWD caused by prions

The increased infectiousness of CWD has resulted in an increasing number of CWD-infected cervids in at least 30 U.S. states and three Canadian provinces. The import of diseased animals from North America has also introduced CWD into South Korea. In addition to cervids, CWD has also been detected in free-ranging Norwegian reindeer, moose, red deer, and reindeer from Sweden, Norway, and Finland.

The application of genetically modified CWD-susceptible mice expressing cervid PrP^C (CerPrP^C) has provided important insights into varied aspects of disease pathogenesis. For example, it was observed that North American moose and deer encode glutamine (Q) at codon 226 (CerPrP-Q226), while elk encode glutamate (E) at this position (CerPrP-E226). The role of these variations in the selection and propagation of CED strains was elucidated in previous studies using transgenic (Tg) mice.

Scientists have also developed CWD-susceptible gene-targeted (Gt) mice, in which the PrP coding sequence was incorporated with CerPrP-Q226 or CerPrP-E226 to determine the effects of primary structural differences. In vivo experiments using Tg mice provided important insights into disease outcomes in the presence of amino acid changes. One of the key advantages of this study was that GT mice recapitulated the lymphotropic properties of CWD strains.

Characterization of a novel CWD strain in moose

A recent Emerging Infectious Diseases journal study characterizes a newly emerged strain of CWD in moose in Finland. In this study, the Finnish moose (M-F1) CWD isolate was obtained from a free-ranging female moose identified as sick. In addition, Norwegian moose CWD isolates M-NO1, M-NO2, and M-NO3 were also obtained, along with North American elk CWD isolate (E-US1).

Certain characteristic features of M-F1 CWD prions were found to overlap with the Norwegian moose CWD. Both M-F1 and the Norwegian moose CWD were propagated in mice expressing CerPrP^C-Q226.

Interestingly, Western and histoblot profiles of M-F1 and M-NO1 CerPrP^Sc could not be differentiated. The authors described M-F1 prions as similar to Norwegian moose CWD prions, which are nonlymphotropic. The nonlymphotropic properties of Finnish and Norwegian moose CWD strains indicate a decrease in infectivity.

Despite the similarities, both strains were found to be different based on their disease kinetics, variable responses to GdnHCl denaturation, and dissimilar neuropathologic lesion profiles. These findings substantiate that Finnish and Norwegian moose CWD prions are different.

The expression of CerPrP^C-Q226 in moose suggests the relatively inefficient transmission of M-F1 prions in GtE. However, similar transmission profiles of TgE (M-F1) and TgQ (M-F1) prions indicate that M-F1 favors conformational conversion of CerPrP^C-Q226 over CerPrP^C-E226, irrespective of whether prions contained CerPrP^Sc-E226 or CerPrP^Sc-Q226.

Conclusions

The current study builds on existing evidence of CWD strains by revealing the differential properties of a newly detected Norwegian strain and North American CWD, thus indicating that both the CWD strains were unrelated. The distinct CWD properties in Nordic moose were explained based on the emergence of divergent strains from unrelated and stochastic conversion events in different animals.

Although M-F1 prions had the capacity of suboptimal propagation using CerPrP^C-E226 as a template for replication, the TgE (M-F1) prions were not capable of further propagation by CerPrP^C-E226. Instead, these prions retained an inclination for conversion of CerPrP^C-Q226.