Abstract
Chronic wasting disease (CWD) is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrPSc, prion infection of the central and peripheral neuroendocrine system, and PrPSc deposition in cardiac muscle. There was also prominent PrPSc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the ‘wasting’ or WST strain of hamster CWD.
Highlights
Chronic wasting disease (CWD) in deer and elk is an emerging prion disease of wildlife in North America
A prion disease characterized by a progressive loss of body mass and cachexia has not been described in any of the prion diseases adapted to Syrian golden hamsters (SGH) even though it is a prominent feature of CWD in cervids
Serial passage of CWD into TgMo-sghPrP resulted in an average incubation period of between 187 to 198 days that when serially passaged into SGH resulted in a longer average incubation period between 322 and 389 days even though both rodent species have a similar prion protein gene (Prnp) genotype
Summary
Chronic wasting disease (CWD) in deer and elk is an emerging prion disease of wildlife in North America. CWD is a moderately contagious prion disease in both captive cervid farms and among free-ranging deer [3,4,5]. The epidemiological and experimental data do not indicate that CWD is a zoonotic disease [8,9,10]. This should not be mistaken for definitive evidence that CWD is not zoonotic since the prevalence of CWD continues to increase among free-ranging cervids, and the extent of human exposure to CWD is difficult to estimate. The large number of susceptible cervids, moderate infection rates, and lack of effective strategies to control CWD transmission in wildlife has the potential to give rise to new biological strains whose pathogenicity for humans may be distinct from currently circulating CWD strains
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