Animal Prion Diseases

Amyloid Plaque Aggregation
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Figure 1: Induced BSE and vCJD amyloid plaques in mice. Amyloid plaque is a result of the pathogenesis of BSE [11]

Animal prion disease is a form of neurodegenerative disease that involves the accumulation of the prion protein (PrP). PrP may exist in two forms: a normal cellular prion protein designated as PrPC or a pathogenic misfolded conformation designated as PrPSc [1]. The infectious prion particle is able to cross the species barrier, allowing animal prion diseases to be transmitted to humans and cause neurodegenerative diseases. These neurodegenerative diseases are incurable, with pathogenesis in the central nervous system that slowly leads to fatality[2]. Animal prion diseases that are most relevant to human health security are bovine spongiform encephalopathy (BSE), chronic wasting disease (CWD) and scrapie. Although all of these diseases are dependent on PrPSc, their symptoms are varied and unique. These specific diseases are of the most concern because the animals that act as a vector for PrPSc are in regular human proximity. As a result, understanding the pathogenesis and the ability of the disease to use animals as reservoirs for PrPSc contributes to identifying effective methods to combat animal prion disease.

Animal Prion Diseases

Bovine Spongiform Encephalopathy (BSE)

Bovine Spongiform Encephalopathy Overview
Figure 2: Introduction to how BSE infects cows, affects humans, and how BSE symptoms appear[9].

Bovine spongiform encephalopathy (BSE) or more commonly known as "mad cow disease" is a type of neurodegenerative animal prion disease that affects cattle. There are two strains of BSE being typical BSE and atypical BSE. Typical BSE is linked to variant Creutzfeldt-Jakob Disease (vCJD) and has been preventable through the removal of contaminated feed whereas atypical BSE is theorized to have been risen spontaneously[2]. Strong evidence has shown that the origin to typical BSE infection was the use of contaminated meat and bone meal mixed into cattle feed[1]. As a result, more effort has been put to controlling typical BSE infection through control measures on cattle feed. Clinical symptoms of BSE may include tremors, gait abnormalities of the hind limb (ataxia), aggressive behavior, apprehension, and hyper reactivity to stimuli[1]. The ability of the PrPSc to infect the beef humans consume presents a huge risk towards human health.

Chronic Wasting Disease (CWD)

Chronic Wasting Disease Overview
Figure 3: A documentary introduction with facts, symptoms and concerns regarding CWD [10].

Chronic wasting disease (CWD) is a type of neurodegenerative animal prion disease that primarily affects the family Cervidae such as deer, elk, moose and mules [2]. It is possible for the infection to have a huge range of incidence within a herd ranging from 0.1%, 50% and 100%[1]. The disease is progressive and the symptoms increase with time to fatality. The symptoms also make the affected animals more susceptible to predation therefore transferring the infectious agent to other animals. Clinical symptoms of CWD are apparent in adults and range between behavioural abnormalities and physical changes. Symptoms may include dramatic and progressive weight loss, blank facial expressions, drooped ears, decreased social interactions, increased salivation, polydipsia, polyuria, repetitive movement patterns, etc [2]. Human interaction with CWD deer is primarily through hunters. The ability for PrPSc to remain in uncontrolled wild environments via host shedding may prompt future infections if left unchecked and more research is required to see if CWD is transmissible to humans


Scrapie is a neurodegenerative disease that affects primarily sheep and goats. The name of the disease is derived from the behaviour pattern of the infected animals where they develop a compulsion to scrape their fleece against rocks, trees, or farm fences in an effort to relieve themselves of an itching sensation known as pruritus[2]. Like BSE, Scrapie can be divided into typical scrapie and atypical scrapie and although there is much overlap between the two types, differentiation is based off the major symptoms. The major clinical symptoms of atypical scrapie are ataxia, lack of coordination with the absence of pruritus whereas the typical scrapie symptom is the appearance of the aforementioned itching behaviour[1]. Other clinical symptoms include convulsive collapsing, gaits and excessive lip smacking[2]. The incubation of the scrapie agent can range from two to five years with fatality occurring within two weeks to six months following the appearance of symptoms resulting in a 3-5% mortality rate of sheep flocks annually[1]. The large of amount of sheep and goat interaction with humans prompts further research in quick detection of PrPSc.

Understanding Animal Prion Disease: Transmission and Pathogenesis

Sympathetic and Parasympathetic Manipulation (BSE)

PrPSc's ability to use the sympathetic and parasympathetic nervous system to reach the CNS
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Figure 4: Overview of the pathways of PrPSc infection in BSE cattle with all key CNS structures involved. Red circles denote PrPSc infections sites [13]

The primary method of infection is through contaminated cattle feed that has come into contact with PrPSc as there is no direct evidence of maternal transmission[2]. In order for humans to be infected with BSE, they must consume infected meat as BSE is transmitted orally and not through direct contact[2]. Evidence for this is that no PrPSc activity is found in milk, semen or embryos but the infectious agent can be found in the tonsils, ileum, adrenal glands, spinal cord, muscle, fat and the dorsal root, trigeminal and thoracic ganglia[1]. Pathogenesis involves the autonomic nervous system (ANS) and gastrointestinal tract (GIT) [8]which allows PrPSc to reach the central nervous system (CNS) via two pathways. It can reach the CNS through retrograde invasion of either the parasympathetic GIT innervations fibres (vagus nerve) or the manipulation of the sympathetic GIT innervation complex (splanchic nerves, lumbal/caudal thoracic spinal cord and celiac and mesenteric ganglion system)[8]. Fatality is reached 6 months after the onset of symptoms as a consequence to the spongiois and buildup of amyloid plaque due to protein misfolding[2].

Lymphoreticular system with peripheral tissue infectivity (CWD)

Horizontal transmission is the primary method of infection as the PrPSc is shed into the environment by infected hosts and then transmitted to uninfected hosts through the nasal and oral pathways[6]. Environmental shedding is not the only method however as possible consumption of infected deer has been considered but requires more research. The infectious prion is found throughout the entire body with the central nervous system containing the highest levels of PrPSc activity. Although the CNS contains the most infectious section of the animal, peripheral tissues like muscle, fat, and lymph nodes are more accessible for predation and consumption with feline predators, such as the cougar, showing levels of the PrPSc agent in their system[4]. More research is required for understanding the methods of physiological pathogenesis but it has been theorized that the lymphoreticular system is involved in a similar fashion to BSE and Scrapie[1]. The capacity for CWD to be transmitted towards humans is still a topic of research and a recent paper by Race et al.looked at whether fat tissue from CWD deer could infect deer prion protein expressing mice. The results implied that the degree of infectivity within fat increases as CWD reaches late stages4 so fat tissue has the capability to be infection to other animals (i.e., mice)[4]. As a result of the disease’s pathogenesis the CNS of affected cervids have shown intraneuronal vacuolation, neuronal degeneration, hypertrophy of astrocytes, amyloid plaques and spongiform lesions of various neuroanatomical structures such as the thalamus, hypothalamus, cortex, pons, midbrain and medulla oblongata[1].

GALT and lymphoid network (Scrapie)

PrPSc infections of lymph nodes
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Figure 5: Immunostaining of different lymph nodes that show PrPSc in an infected lamb [12]

Like CWD, horizontal transmission is the main method of infection. However, unlike cattle and deer, sheep are used for more economical purposes rather than consumption. As a result, infection is done through various bodily secretions. The treatment of sheep for their wool puts high PrPSc level secretions and susceptible human tissue in a close proximity range. As a result rapid diagnostic testing of the third eyelid is used to determine PrPSc levels of infectivity quickly[1]. PrPSc enters the oral pathway through grazing and proceeds to infect the palatine tonsil region and eventually the Peyers patches of the gut-associated lymphoid tissues (GALT)[7]. Following initial infection, PrPSc can be found in the surrounding lymphoid network of infection sites while travelling through efferent parasympathetic and sympathetic nerve fibers of the gut to the CNS[7]. Spongiform vacuolation, astrogliosis and infectious prion aggregation in the form of amyloid plaques within the CNS are all the result of pathogenesis[1]. Similar to BSE and CWD, the infectious prion can be found in peripheral tissues like the tonsils, spleen, lymph nodes, muscles, placenta and proximal colon[1].

Prion Reservoirs in the Environment

Animal Mortality and Infected Host Shedding

Unchecked animal mortality of infected animals contributes to the preservation of prions within the environment as carcasses become larges deposits of infectious matter that will pass on through the ecosystem via scavengers. Out of the mentioned animal prion diseases, CWD transmission is most dependent on shedding within the environment. The ability of the infectious agent in CWD to be found in a large variety of host tissue such as the kidney, skeletal and cardiac muscle, lymphoreticular system, gastrointestinal, etc. allows CWD PrPSc to have access to a large variety of organs for its transmission[5]. Saliva, urine and feces from infected animals can be released into the environment as a contamination factor forming prion infectivity zones[5]. Detection within the environment is difficult due to the amount of information that needs to be assessed as western blots cannot provide information pertaining to the levels of infectivity and animal bioassays are improbable for the amount of environmental samples needed[3].

Soil Binding

Prions and Soil Binding
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Figure 6: The various factors that must be accounted for when assessing the ability of prions binding to soil and how it affects prions.[14].

Furthermore, the ability of prions to bind to soil components increases the chance of future infection and its persistent presence within the environment. Studies have shown that prions maintain their infectivity when bound to minerals (i.e. quartz, clay, etc) and this interaction is possible through the positively charged peptides of the prion and the negatively charged mineral surface. The electrostatic forces involved in binding allow it to not only be a highly irreversible process but a rapid one at that. The ability of a prion to be infectious is dependent on its conformation structure so infectivity has the possibility to either increase or decrease. Regardless of infectivity, the prion-soil binding factor allows PrPSc to endure in the environment and create subsequent infections [3].

Combating Animal Prion Disease

Genetic Polymorphisms and Selective Breeding

With a focus of PrP encoding genes (PRNP), work with genetics has been done to identify whether the susceptibility to these diseases has any genetic basis with insertion/deletions (indels). Susceptibility to BSE has been shown to 3 variations of the PRNP gene; a 23 basepair indel of the promoter, a 12 baspair indel of the first intron and an EK211K polymorphism. PRNP polymorphisms associated with CWD resistance in the cervidae family are S96G, M132L and S225F. In terms of Scrapie sheep and the PrP encoding genes, a Q171R polymorphism has been shown to increase scrapie resistance whereas an A136V polymorphism implies increased scrapie susceptibility. Although these finding provide promise for possibly attaining a new control measure for the diseases through selective breeding, more research is required as environmental factors must be considered as well[1].

Eradication, Burial and Incineration

Eradication and burial of infected animals was the first employed method when dealing with animal prion diseases. After such measures, farmers and cattle ranchers would continue to use the land of past infection incidents completely unaware that prions remained within the soil. As a result animals re-exposed to the incident areas were infected again by the same prions[3] would presume the slaughter and burial of infected animals an incompetent method. Incineration is the most effective method of combating prion disease as a high temperature of 1000 degrees Celsius is necessary to destroy prion infectivity because low infectivity still persists even after exposure to 600 degrees Celsius[3]. The capacity to withstand such temperatures rests with the conformational structure of the prion as an intense heat is needed to denature the protein. Attractive as the concept of incineration may be, the application of incineration is highly impractical because prions still exists within the environment if shedding has occurred from infected animals. The collateral damage to the environment if the entire affected area undergoes mass incineration would be deemed unviable.

1. Imran, M., & Mahmood, S. (2011). An overview of animal prion diseases. Virol J, 8, 493.
2. Londhe, M. S., Mahajan, N. K., Gupta, R. P. & Londhe, R. M. (2012) Review on prion diseases in animals with emphasis to Bovine Spongiform Encephalopathy. Veterinary World, 5 (7), 443-448.
3. Saunders, S. E., Bartelt-Hunt, S. L., & Bartz, J. C. (2008). Prions in the environment. Prion, 2(4), 162-169.
4. Race, B., Meade-White, K., Race, R., & Chesebro, B. (2009). Prion infectivity in fat of deer with chronic wasting disease. Journal of virology, 83(18), 9608-9610.
5. John, T. R., Schätzl, H. M., & Gilch, S. (2013). Early detection of chronic wasting disease prions in urine of pre-symptomatic deer by real-time quaking-induced conversion assay. Prion, 7(3), 253.
6. Saunders, S. E., Bartelt-Hunt, S. L., & Bartz, J. C. (2012). Occurrence, transmission, and zoonotic potential of chronic wasting disease. Emerg Infect Dis, 18(3), 369-376.
7. Van Keulen, L. J. M., Vromans, M. E. W., & Van Zijderveld, F. G. (2002). Early and late pathogenesis of natural scrapie infection in sheep. Apmis, 110(1), 23-32.
8. Hoffmann, C., Ziegler, U., Buschmann, A., Weber, A., Kupfer, L., Oelschlegel, A., & Groschup, M. H. (2007). Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy. Journal of general virology, 88(3), 1048-1055.
11. Adapted from “compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans” by Scott. M., 1999. Proceedings of the National Academy of Sciences , 96(26), p. 15137–15142. Copyright 1999 by PNAS
12. Adapted from “Early and late pathogenesis of natural scrapie infection in sheep” by Van Keulen et al, 2002. Apmis, 110(1), 23-32. Copyright 1999-2014 by John Wiley & Sons, Inc
13. Adapted from “Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy” by Hoffmann et al, 2007. Journal of general virology, 88(3), 1048-1055. Copyright 2014 by Society of General Microbiology
14. Adapted from “Prions in the environment” by Saunders et al., 2008. Prion, 2(4), 162-169. Copyright 2008 by Landes Bioscience

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