Prion-protein-related diseases of animals and man

Variant Form ◽

Peripheral Tissues ◽

Disease Characteristics ◽

Jakob Disease ◽

The Central Nervous System ◽

Iatrogenic Transmission

Scrapie, bovine spongiform encephalopathy (BSE), Creutzfeldt–Jakob disease (CJD), and related diseases of mink (transmissible mink encephalopathy), mule deer and elk (chronic wasting disease) are the founder members of a group of diseases called the transmissible degenerative (or spongiform) encephalopathies (TSE). These diseases can be transmitted by prions from affected to healthy animals by inoculation or by feeding diseased tissues. Prions are cellular proteins that can transfer metabolic and pathological phenotypes vertically from parent to progeny or horizontally between cells and animals. TSEs are characterised by the accumulation of the prion form of the mammalian prion protein (PrPC) in the central nervous system or peripheral tissues of animals and humans. Mutations of the human PrP gene are linked to rare, familial forms of disease and prion-protein gene polymorphisms in humans and other species are linked to survival time and disease characteristics in affected individuals. Iatrogenic transmission of CJD in man has occurred, and a variant form of CJD (vCJD) is due to cross-species transmission of BSE from cattle to humans. Atypical forms of scrapie and BSE have been identified during large-scale monitoring for TSEs worldwide. This chapter outlines our current understanding of scrapie, BSE, CJD and other TSEs and highlights recent progress in defining the role in disease of the prion protein, PrP.

Prion protein genetics: Host PrP control of TSE susceptibility

The Biochemist ◽

10.1042/bio02704020 ◽

2005 ◽

Vol 27 (4) ◽

pp. 20-23

Author(s):

Wilfred Goldmann

Keyword(s):

Prion Protein ◽

Degenerative Disorders ◽

Jakob Disease ◽

The Central Nervous System ◽

Important Host ◽

Disease Family ◽

Sheep Scrapie

TSEs (transmissible spongiform encephalopathies) are fatal, degenerative disorders of the central nervous system. The best-known members of this disease family are sheep scrapie, cattle BSE (bovine spongiform encephalopathy) and human CJD (Creutzfeldt–Jakob disease). By far the most important host gene in TSEs is the PrP (prion protein) gene. It modulates TSE susceptibility at many levels and is the crucial element in the treatment and eradication of these diseases. This article will highlight the advances in our understanding of PrP genetics in animals and man.

Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein

Journal of General Virology ◽

10.1099/vir.0.042507-0 ◽

2012 ◽

Vol 93 (7) ◽

pp. 1624-1629 ◽

Cited By ~ 52

Author(s):

Rona Wilson ◽

Chris Plinston ◽

Nora Hunter ◽

Cristina Casalone ◽

Cristiano Corona ◽

...

Keyword(s):

Bovine Spongiform Encephalopathy ◽

Prion Protein ◽

Chronic Wasting Disease ◽

Wild Type ◽

Wasting Disease ◽

Jakob Disease ◽

Human Prion Protein

The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt–Jakob disease (vCJD) has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several novel TSEs in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. In this study, we inoculated two forms of atypical BSE (BASE and H-type BSE), a chronic wasting disease (CWD) isolate and seven isolates of atypical scrapie into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP). Upon challenge with these ruminant TSEs, gene-targeted Tg mice expressing human PrP did not show any signs of disease pathology. These data strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans.

Detection and Analysis of Animal Materials in Food and Feed

Journal of Food Protection ◽

10.4315/0362-028x-63.11.1602 ◽

2000 ◽

Vol 63 (11) ◽

pp. 1602-1609 ◽

Cited By ~ 42

Author(s):

DRAGAN MOMCILOVIC ◽

AVRAHAM RASOOLY

Keyword(s):

Animal Feed ◽

Neurological Diseases ◽

Variant Form ◽

Food And Feed ◽

Ruminant Animals ◽

Jakob Disease ◽

Animal Material

Bovine spongiform encephalopathy (BSE) belongs to a group of progressively degenerative neurological diseases known as transmissible spongiform encephalopathies (TSEs) associated with a variant form of Creutzfeldt-Jakob disease in humans. TSEs are fatal diseases caused by prions (proteinaceous infectious particle) and are characterized by an incubation period that may range from several months to several years, depending on the host. Because BSE is spread through animal feed, the main strategy for preventing the establishment and spread of BSE is to prohibit the use of proteins derived from mammalian tissue in feed for ruminant animals. Enforcement of these regulations relies on the ability to identify the presence of prohibited proteins in ruminant feed. The methods to detect bovine products in rendered and cooked materials are based on analyses of DNA, bone, or protein. In this article, we discuss the current methodology as well as other potentially useful methods of analysis of animal material in food. While methods are generally useful, none specifically distinguish between prohibited bovine material and allowable bovine products, such as milk or blood. Furthermore, all these methods are hampered by the fact that the rendering process involves heat treatment that denatures and degrades proteins and DNA. There is a need for improving existing methods and developing new methods to overcome these two limitations.

PMCA Applications for Prion Detection in Peripheral Tissues of Patients with Variant Creutzfeldt-Jakob Disease

Biomolecules ◽

10.3390/biom10030405 ◽

2020 ◽

Vol 10 (3) ◽

pp. 405 ◽

Cited By ~ 2

Author(s):

Giorgio Giaccone ◽

Fabio Moda

Keyword(s):

Protein Misfolding ◽

Prion Diseases ◽

Disease Diagnosis ◽

Diagnostic Techniques ◽

Variant Form ◽

Definite Diagnosis ◽

Peripheral Tissues ◽

New Variant ◽

Jakob Disease

Prion diseases are neurodegenerative and invariably fatal conditions that affect humans and animals. In particular, Creutzfeldt-Jakob disease (CJD) and bovine spongiform encephalopathy (BSE) are paradigmatic forms of human and animal prion diseases, respectively. Human exposure to BSE through contaminated food caused the appearance of the new variant form of CJD (vCJD). These diseases are caused by an abnormal prion protein named PrPSc (or prion), which accumulates in the brain and leads to the onset of the disease. Their definite diagnosis can be formulated only at post-mortem after biochemical and neuropathological identification of PrPSc. Thanks to the advent of an innovative technique named protein misfolding cyclic amplification (PMCA), traces of PrPSc, undetectable with the standard diagnostic techniques, were found in peripheral tissues of patients with vCJD, even at preclinical stages. The technology is currently being used in specialized laboratories and can be exploited for helping physicians in formulating an early and definite diagnosis of vCJD using peripheral tissues. However, this assay is currently unable to detect prions associated with the sporadic CJD (sCJD) forms, which are more frequent than vCJD. This review will focus on the most recent advances and applications of PMCA in the field of vCJD and other human prion disease diagnosis.

Pathological prion protein in muscles of hamsters and mice infected with rodent-adapted BSE or vCJD

Journal of General Virology ◽

10.1099/vir.0.81277-0 ◽

2006 ◽

Vol 87 (1) ◽

pp. 251-254 ◽

Cited By ~ 22

Author(s):

Achim Thomzig ◽

Franco Cardone ◽

Dominique Krüger ◽

Maurizio Pocchiari ◽

Paul Brown ◽

...

Keyword(s):

Public Health ◽

Prion Protein ◽

Health Risks ◽

Mammalian Muscle ◽

Public Health Risks ◽

Jakob Disease ◽

First Time

Recently, pathological prion protein (PrPTSE) was detected in muscle from sheep infected with scrapie, the archetype of transmissible spongiform encephalopathies (TSEs). This finding has highlighted the question of whether mammalian muscle may potentially also provide a reservoir for TSE agents related to bovine spongiform encephalopathy (BSE) and variant Creutzfeldt–Jakob Disease (vCJD). Here, results are reported from studies in hamsters and mice that provide direct experimental evidence, for the first time, of BSE- and vCJD-associated PrPTSE deposition in muscles. Our findings emphasize the need for further assessment of possible public-health risks from TSE involvement of skeletal muscle.

Genetic Factors in Mammalian Prion Diseases

Annual Review of Genetics ◽

10.1146/annurev-genet-120213-092352 ◽

2019 ◽

Vol 53 (1) ◽

pp. 117-147 ◽

Cited By ~ 10

Author(s):

Simon Mead ◽

Sarah Lloyd ◽

John Collinge

Keyword(s):

Prion Protein ◽

Prion Disease ◽

Protein Interactions ◽

Prion Diseases ◽

Cellular Prion Protein ◽

Cellular Functions ◽

Modifying Factors ◽

Jakob Disease ◽

The Central Nervous System

Mammalian prion diseases are a group of neurodegenerative conditions caused by infection of the central nervous system with proteinaceous agents called prions, including sporadic, variant, and iatrogenic Creutzfeldt-Jakob disease; kuru; inherited prion disease; sheep scrapie; bovine spongiform encephalopathy; and chronic wasting disease. Prions are composed of misfolded and multimeric forms of the normal cellular prion protein (PrP). Prion diseases require host expression of the prion protein gene ( PRNP) and a range of other cellular functions to support their propagation and toxicity. Inherited forms of prion disease are caused by mutation of PRNP, whereas acquired and sporadically occurring mammalian prion diseases are controlled by powerful genetic risk and modifying factors. Whereas some PrP amino acid variants cause the disease, others confer protection, dramatically altered incubation times, or changes in the clinical phenotype. Multiple mechanisms, including interference with homotypic protein interactions and the selection of the permissible prion strains in a host, play a role. Several non- PRNP factors have now been uncovered that provide insights into pathways of disease susceptibility or neurotoxicity.

Retinal Function and Morphology Are Altered in Cattle Infected with the Prion Disease Transmissible Mink Encephalopathy

Veterinary Pathology ◽

10.1354/vp.08-vp-0206-w-fl ◽

2009 ◽

Vol 46 (5) ◽

pp. 810-816 ◽

Cited By ~ 12

Author(s):

J. D. Smith ◽

J. J. Greenlee ◽

A. N. Hamir ◽

J. A. Richt ◽

M. H. West Greenlee

Keyword(s):

Prion Protein ◽

Specific Effect ◽

Retinal Function ◽

Implicit Time ◽

Variant Form ◽

Infected Cattle ◽

Transmissible Mink Encephalopathy

Transmissible spongiform encephalopathies (TSEs) are a group of diseases that result in progressive and invariably fatal neurologic disease in both animals and humans. TSEs are characterized by the accumulation of an abnormal protease-resistant form of the prion protein in the central nervous system. Transmission of infectious TSEs is believed to occur via ingestion of prion protein–contaminated material. This material is also involved in the transmission of bovine spongiform encephalopathy (“mad cow disease”) to humans, which resulted in the variant form of Creutzfeldt-Jakob disease. Abnormal prion protein has been reported in the retina of TSE-affected cattle, but despite these observations, the specific effect of abnormal prion protein on retinal morphology and function has not been assessed. The objective of this study was to identify and characterize potential functional and morphologic abnormalities in the retinas of cattle infected with a bovine-adapted isolate of transmissible mink encephalopathy. We used electroretinography and immunohistochemistry to examine retinas from 10 noninoculated and 5 transmissible mink encephalopathy–inoculated adult Holstein steers. Here we show altered retinal function, as evidenced by prolonged implicit time of the electroretinogram b-wave, in transmissible mink encephalopathy–infected cattle before the onset of clinical illness. We also demonstrate disruption of rod bipolar cell synaptic terminals, indicated by decreased immunoreactivity for the alpha isoform of protein kinase C and vesicular glutamate transporter 1, and activation of Müller glia, as evidenced by increased glial fibrillary acidic protein and glutamine synthetase expression, in the retinas of these cattle at the time of euthanasia due to clinical deterioration. This is the first study to identify both functional and morphologic alterations in the retinas of TSE-infected cattle. Our results support future efforts to focus on the retina for the development of new strategies for the diagnosis of TSEs.

Sporadic Creutzfeldt-Jakob Disease: Diagnosing Typical and Atypical Presentations under Limited Circumstances

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000514470 ◽

2021 ◽

pp. 1-7

Author(s):

Shazma Khan ◽

Sara Khan

Keyword(s):

Developing Countries ◽

Brain Mri ◽

Tertiary Care ◽

Rapid Onset ◽

Care Hospital ◽

Jakob Disease ◽

The Central Nervous System ◽

Missed Diagnosis ◽

Atypical Presentations

Introduction: Sporadic Creutzfeldt-Jakob disease (sCJD) is a transmissible disorder of the central nervous system caused by the transformation of normal prion protein into an abnormal misfolded form. The process begins spontaneously and runs a vicious cycle to cause spongiform encephalopathy, rapidly resulting in death. Amply described in the western literature, CJD is scarcely reported in Asia due to certain limitations including missed diagnosis, under-reporting, and rarity of the disease. Brain MRI, electroencephalogram, cerebrospinal fluid testing, and biopsy of the infected brain tissue support the diagnosis in cases of clinical suspicion. However, the diagnosis can still be made with limited available resources in developing countries. Method: A review of CJD cases evaluated in the neurology department of a tertiary care hospital in Pakistan was done from 2002 to 2018. Results: Eleven cases labeled as sCJD are identified based on the European MRI-CJD consortium criteria. This is the first study on CJD from Pakistan, which includes both the typical and atypical presentations. Conclusion: Even with limited testing available, the diagnosis of CJD can be made with confidence in the developing countries, provided the suspicion is kept high in cases of rapid onset dementia and acute behavioral changes.

Presence of subclinical infection in gene-targeted human prion protein transgenic mice exposed to atypical bovine spongiform encephalopathy

Journal of General Virology ◽

10.1099/vir.0.052738-0 ◽

2013 ◽

Vol 94 (12) ◽

pp. 2819-2827 ◽

Cited By ~ 11

Author(s):

Rona Wilson ◽

Karen Dobie ◽

Nora Hunter ◽

Cristina Casalone ◽

Thierry Baron ◽

...

Keyword(s):

Human Health ◽

Bovine Spongiform Encephalopathy ◽

Prion Protein ◽

Disease Transmission ◽

Large Scale ◽

Single Agent ◽

Diagnostic Methods ◽

Human Prion Protein

The transmission of bovine spongiform encephalopathy (BSE) to humans, leading to variant Creutzfeldt–Jakob disease has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health. Until recently, TSE disease in cattle was thought to be caused by a single agent strain, BSE, also known as classical BSE, or BSE-C. However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. To model the risk to human health, we previously inoculated these two forms of atypical BSE (BASE and BSE-H) into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP) (HuTg) but were unable to detect any signs of TSE pathology in these mice. However, despite the absence of TSE pathology, upon subpassage of some BASE-challenged HuTg mice, a TSE was observed in recipient gene-targeted bovine PrP Tg (Bov6) mice but not in HuTg mice. Disease transmission from apparently healthy individuals indicates the presence of subclinical BASE infection in mice expressing human PrP that cannot be identified by current diagnostic methods. However, due to the lack of transmission to HuTg mice on subpassage, the efficiency of mouse-to-mouse transmission of BASE appears to be low when mice express human rather than bovine PrP.

How to Limit the Spread of Creutzfeldt-Jakob Disease

Infection Control and Hospital Epidemiology ◽

10.1017/s0195941700004720 ◽

1996 ◽

Vol 17 (8) ◽

pp. 521-528

Author(s):

Dominique Dormont

Keyword(s):

Blood Donation ◽

Transmissible Spongiform Encephalopathy ◽

Infected Individual ◽

Experimental Models ◽

Corneal Grafting ◽

Jakob Disease ◽

Spleen And Lymph Nodes

AbstractTransmissible spongiform encephalopathies are rare lethal diseases induced in humans and animals by unconventional agents called transmissible spongiform encephalopathy agents (TSEAs), virions, or prions. Several cases of iatrogenic Creutzfeldt-Jakob disease (CJD) have been reported in the literature after neuro-surgery, treatment with pituitary-derived hormones, corneal grafting, and use of dura mater lyophilisates. In a given infected individual, TSEA-associated infectiousness depends on the nature of the organ: the central nervous system has the highest infectiousness, spleen and lymph nodes a medium infectiousness, and organs such as bone, skin, or skeletal muscles do not harbor any detectable infectiousness in experimental models. Transmissible spongiform encephalopathy/prions have unconventional properties; in particular, they resist almost all the chemical and physical processes that inactivate conventional viruses. Therefore, prevention of CJD agent transmission must be taken into account in daily hospital practice. Efficient sterilization procedures should be determined. In tissue and blood donation, donors with a neurologic history must be excluded, and patients treated with pituitary-derived hormones should be considered potentially infected with TSEA and excluded.