Evaluation of the zoonotic potential of transmissible mink encephalopathy TSE Prion disease


Title: Evaluation of the zoonotic potential of transmissible mink


item Comoy, Emmanuel - item Mikol, Jacqueline - item Ruchoux, Marie-Madeleine - item Durand, Valerie - item Luccantoni-Freire, Sophie - item Dehen, Capucine - item Correia, Evelyne - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Torres, Juan Maria - item Brown, Paul - item Deslys, Jean-Philippe -

Submitted to: Pathogens Publication Type: Peer Reviewed Journal Publication Acceptance Date: July 30, 2013 Publication Date: July 30, 2013 Citation: Comoy, E.E., Mikol, J., Ruchoux, M., Durand, V., Luccantoni-Freire, S., Dehen, C., Correia, E., Casalone, C., Richt, J.A., Greenlee, J.J., Torres, J.M., Brown, P., Deslys, J. 2013. Evaluation of the zoonotic potential of transmissible mink encephalopathy. Pathogens. 2:(3)520-532.

Interpretive Summary: Cases of bovine spongiform encephalopathy (BSE) or mad cow disease can be subclassified into at least 3 distinct disease forms with the predominate form known as classical BSE and the others collectively referred to as atypical BSE. Atypical BSE can be further subdivided into H-type and  L-type cases that are distinct from classical BSE and from each other. Both of the atypical BSE subtypes are believed to occur spontaneously, whereas classical BSE is spread through feeding contaminated meat and bone meal to cattle. Transmissible mink encephalopathy (TME) is another prion disease that transmits to cattle and show similarities to L-type BSE when subjected to laboratory testing. The purpose of this study was to use non-human primates (cynomologous macaque) and transgenic mice expressing the human prion protein to determine if TME could represent a potential risk to human health. TME from two sources (cattle and raccoons) was able to infect non-human primates and transgenic mice after exposure by the intracranial route. This result suggest that humans may be able to replicate TME prions after an exposure that allows infectious material access to brain tissue. At this time, it is unknown whether non-human primates or transgenic mice would be susceptible to TME prions after oral exposure. The results obtained in these animal models were similar to those obtained for L-type BSE. Although rare, the existence of TME and that it transmits to cattle, non-human primates, and transgenic mice suggest that feed bans preventing the feeding of mammalian tissues to cattle should stay in place and that regular prion surveillance during the slaughter should remain in place. Parties with  interest in the cattle and beef industries and regulatory officials responsible for safe feeding practices of cattle will be interested in this work. Technical Abstract: Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis to the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques assume a low cattle-to-primate species barrier: we therefore evaluated the zoonotic potential of cattle-adapted TME. In less than two years, this strain induced in cynomolgus macaques a neurological disease similar to L-BSE and distinct from c-BSE. TME derived from another donor species (raccoon) induced a similar disease with shorter incubation periods. L-BSE and cattle-adapted TME were also transmissible to transgenic mice expressing human PrP. Interestingly, secondary transmissions to transgenic mice expressing bovine PrP showed the maintenance of prion strain features for the three tested bovine prion strains (cattle TME, c-BSE and L-BSE) regardless of intermediate host. Thus, TME is the third animal prion strain transmissible to both macaques and humanized transgenic mice, suggesting zoonotic potentials that should be considered in the risk analysis of animal prion diseases for human health. Moreover, the similarities between TME and L-BSE are highly suggestive of a link between those strains, and of the presence of L-BSE decades prior to its identification in USA and Europe.


Research Project: Transmission, Differentiation, and Pathobiology of Transmissible Spongiform Encephalopathies Project Number: 3625-32000-103-00 Project Type: Appropriated

Start Date: Oct 01, 2011 End Date: Sep 30, 2016

Objective: 1. Investigate the pathobiology of atypical transmissible spongiform encephalopathies (TSEs) in natural hosts. A. Investigate the pathobiology of atypical scrapie. B. Investigate the pathobiology of atypical bovine spongiform encephalopathy (BSE). 2. Investigate the horizontal transmission of TSEs. A. Assess the horizontal transmission of sheep scrapie in the absence of lambing. B. Determine routes of transmission in chronic wasting disease (CWD) infected premises. C. Assess oral transmission of CWD in reindeer. 3. Investigate determinants of CWD persistence. A. Determine CWD host range using natural routes of transmission. B. Investigate the pathobiology of CWD.

Approach: The studies will focus on three animal transmissible spongiform encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic wasting disease (CWD) of deer, elk, and moose. The research will address sites of accumulation, routes of infection, environmental persistence, and ante mortem diagnostics with an emphasis on controlled conditions and natural routes of infection. Techniques used will include clinical exams, histopathology, immunohistochemistry and biochemical analysis of proteins. The enhanced knowledge gained from this work will help mitigate the potential for unrecognized epidemic expansions of these diseases in populations of animals that could either directly or indirectly affect food animals.


Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed. ***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat



EFSA Journal 2011 The European Response to BSE: A Success Story

This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;

Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story


EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.




see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;


*** 2010-2011 ***

When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.


Monday, September 26, 2011 L-BSE BASE prion and atypical sporadic CJD


Transmission of Atypical Italian sCJD Case to Humanized Mice Reveals a Novel Infectious Strain

Roberta Galeno,1,† Marco Sbriccoli,1 Loredana Ingrosso,1 Silvia Graziano,1 Angelina Valanzano,1 Anna Poleggi,1 Angela De Pascalis,1 Anna Ladogana,1 Franco Cardone,1 Maria Puopolo,1 Gianluigi Zanusso2 and Maurizio Pocchiari1

1Istituto Superiore di Sanità; Rome, Italy; 2University of Verona; Verona, Italy†Presenting author; Email: [email protected]

Sporadic Creutzfeldt-Jakob disease (sCJD) is a neurodegenerative prion disorder with uncertain etiology characterized by a typical combination of clinical symptoms, neuropathological lesions, and by the deposition of the pathological protein PrPTSE in the brain.

The vast majority of patients affected by sCJD can be categorized according to the genotype at the polymorphic position www.landesbioscience.com Prion 127

129 of PrP (methionine or valine) and to the molecular mass of PrPTSE (type 1 or 2, corresponding to 21 or 19 kDa), yielding six possible combinations (MM1, MM2, VV1, VV2, MV1, and MV2) that associate with five clinico-pathological variants. Transmission studies of these sCJD subtypes into transgenic mice expressing the human prion protein allowed to identify four different infectious strains, which can partly explain the heterogeneity observed in sCJD patients.1

We recently described a novel molecular and pathological phenotype of sCJD (MV at position 129 of PrP), associated with an unprecedented electrophoretic pattern of PrPTSE characterized by the absence of the highly glycosylated isoform. In this work, we sought to characterize the prion strain associated with this atypical case by intracerebral inoculation into gene-targeted transgenic mice (HuTg) carrying the human PRNP gene with the three 129 genotype combinations. For comparison, three Italian sCJD cases heterozygous at position 129 of the prion protein, belonging to different subtypes (MV1, MV1/2, MV2), were transmitted to the same panel of transgenic mice. Survival times, attack rates, lesion profiles, and molecular analysis of the PrPTSE type recovered from mouse brains injected with the atypical case were compared with data from control animals. Mice inoculated with the atypical case displayed a restricted host tropism, with only a small number of VV animals that resulted PrPTSE-positive after an exceedingly long survival time. Interestingly, PrPTSE accumulated in brains from these mice lacks the diglycosylated band similar to that in sCJD inoculum, yet dissimilar to any other PrPTSE observed in HuTg mice by us and by other authors.1,2 Overall, these results strongly indicate that our atypical case associates with a new infectious strain of sCJD. Further investigations are needed to understand the possible connection with other human and animal prion diseases.


1. Bishop MT, Will RG, Manson JC. Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties. Proc Natl Acad Sci USA 2010; 107:12005-10.

2. Bishop MT, Hart P, Aitchison L, Baybutt HN, Plinston C, Thomson V, et al. Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 2006; 5:393-8.


Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"


Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque


2011 Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD


Sunday, February 2, 2014

The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy

NOTE Pathology


WHAT about the sporadic CJD TSE proteins ?

WE now know that some cases of sporadic CJD are linked to atypical BSE and atypical Scrapie, so why are not MORE concerned about the sporadic CJD, and all it’s sub-types $$$

Creutzfeldt-Jakob Disease CJD cases rising North America updated report August 2013

*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing an extreme increase of 48% between 2008 and 2010 ***


Sunday, October 13, 2013

*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012


Thursday, January 2, 2014

*** CWD TSE Prion in cervids to hTGmice, Heidenhain Variant Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ???


Friday, January 10, 2014

*** vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial  type prion disease, what it ???


Monday, January 13, 2014

*** Prions in Variably Protease-Sensitive Prionopathy: An Update Pathogens 2013

Pathogens 2013, 2, 457-471; doi:10.3390/pathogens2030457


Wednesday, January 15, 2014



Sunday, January 19, 2014

*** National Prion Disease Pathology Surveillance Center Cases Examined1 as of January 8, 2014 ***


Thursday, January 23, 2014

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]


Saturday, February 01, 2014

vCJD With Extremely Low Lymphoreticular Deposition of Prion Protein MAY NOT HAVE BEEN DETECTABLE


Wednesday, April 24, 2013

Chimpanzees Released After 30 Years Of Testing, Brace Yourself For Smiles

i remember the late great Dr. Gibbs at NIH whom studied transmissible spongiform encephalopathy prion disease his whole life, and was a great scientist, i remember him saying how bad he hated using chimps for research. he grew very close to the chimps, and it disturbed him greatly. i always thought we should use humans instead of chimps. i.e. death row inmates. expose them, study them, compensate their families. this would indeed put to end the controversy and excuse of 'oh, chimps are not humans, study does not hold water' type mentality. of course it would be a voluntary program.

see this moving video here ;


Wednesday, January 01, 2014

Molecular Barriers to Zoonotic Transmission of Prions

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.




----- Original Message -----

From: David Colby

To: [email protected]

Cc: [email protected]

Sent: Tuesday, March 01, 2011 8:25 AM

Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations

Dear Terry Singeltary,

Thank you for your correspondence regarding the review article Stanley Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner asked that I reply to your message due to his busy schedule. We agree that the transmission of CWD prions to beef livestock would be a troubling development and assessing that risk is important. In our article, we cite a peer-reviewed publication reporting confirmed cases of laboratory transmission based on stringent criteria. The less stringent criteria for transmission described in the abstract you refer to lead to the discrepancy between your numbers and ours and thus the interpretation of the transmission rate. We stand by our assessment of the literature--namely that the transmission rate of CWD to bovines appears relatively low, but we recognize that even a low transmission rate could have important implications for public health and we thank you for bringing attention to this matter.

Warm Regards, David Colby


David Colby, PhDAssistant ProfessorDepartment of Chemical EngineeringUniversity of Delaware





Wednesday, September 08, 2010



Thursday, November 21, 2013

Assessing the susceptibility of transgenic mice over-expressing deer prion protein to bovine spongiform encephalopathy



*** These findings are consistent with the hypothesis that kuru originated from chance consumption of an individual with sporadic CJD.

Kuru prions and sporadic Creutzfeldt–Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice

Jonathan D. F. Wadsworth, Susan Joiner, Jacqueline M. Linehan, Melanie Desbruslais, Katie Fox, Sharon Cooper, Sabrina Cronier, Emmanuel A. Asante, Simon Mead, Sebastian Brandner, Andrew F. Hill *, and John Collinge † Author Affiliations

Medical Research Council Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom Communicated by Charles Weissmann, The Scripps Research Institute, Jupiter, FL, January 10, 2008 (received for review October 10, 2007)

Abstract Kuru provides our principal experience of an epidemic human prion disease and primarily affected the Fore linguistic group of the Eastern Highlands of Papua New Guinea. Kuru was transmitted by the practice of consuming dead relatives as a mark of respect and mourning (transumption). To date, detailed information of the prion strain type propagated in kuru has been lacking. Here, we directly compare the transmission properties of kuru prions with sporadic, iatrogenic, and variant Creutzfeldt–Jakob disease (CJD) prions in Prnp-null transgenic mice expressing human prion protein and in wild-type mice. Molecular and neuropathological data from these transmissions show that kuru prions are distinct from variant CJD and have transmission properties equivalent to those of classical (sporadic) CJD prions.

*** These findings are consistent with the hypothesis that kuru originated from chance consumption of an individual with sporadic CJD.


1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.


The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

PMID: 6997404


Wednesday, November 18, 2009

A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure



Sunday, September 1, 2013

 Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy


Sunday, February 2, 2014

The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy

NOTE Pathology


Terry S. Singeltary Sr. Bacliff, Texas USA 77518 [email protected]