sorry i did not see these questions.
scrapie and cwd have some interesting aspects ;
CHRONIC WASTING DISEASE, CWD, AND THE DEER PENS AT THE FOOT HILLS CAMPUS
page 30,
*** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or about that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.
(PLEASE NOTE SOME OF THESE OLD UK GOVERNMENT FILE URLS ARE SLOW TO OPEN, AND SOMETIMES YOU MAY HAVE TO CLICK ON MULTIPLE TIMES, PLEASE BE PATIENT, ANY PROBLEMS PLEASE WRITE ME PRIVATELY, AND I WILL TRY AND FIX OR SEND YOU OLD PDF FILE...TSS)
IN CONFIDENCE
PERCEPTIONS OF UNCONVENTIONAL SLOW VIRUS DISEASES OF ANIMALS IN USA
GAH WELLS
REPORT OF A VISIT TO THE USA APRIL-MAY 1989
collections.europarchive.org/tna/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf now, years later, see the latest studies here on scrapie and cwd ;
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. The purpose of these experiments was to determine susceptibility of white-tailed deer (WTD) to scrapie and to compare the resultant clinical signs, lesions, and molecular profiles of PrPSc to those of chronic wasting disease (CWD). We inoculated WTD intracranially (IC; n = 5) and by a natural route of exposure (concurrent oral and intranasal (IN); n = 5) with a US scrapie isolate. All deer were inoculated with a 10% (wt/vol) brain homogenate from sheep with scrapie (1ml IC, 1 ml IN, 30 ml oral). All deer inoculated by the intracranial route had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues as early as 7 months-post-inoculation (PI) and a single deer that was necropsied at 15.6 months had widespread distribution of PrPSc highlighting that PrPSc is widely distributed in the CNS and lymphoid tissues prior to the onset of clinical signs. IC inoculated deer necropsied after 20 months PI (3/5) had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in WTD after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months. Moreover, western blots (WB) done on brain material from the obex region have a molecular profile similar to CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like. After a natural route of exposure, 100% of WTD were susceptible to scrapie. Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB. Similar to IC inoculated deer, samples from these deer exhibited two different molecular profiles: samples from obex resembled CWD whereas those from cerebrum were similar to the original scrapie inoculum. On further examination by WB using a panel of antibodies, the tissues from deer with scrapie exhibit properties differing from tissues either from sheep with scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive when probed with mAb P4, however, samples from WTD with scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from WTD with scrapie are strongly positive. This work demonstrates that WTD are highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is differentiable from CWD.
www.landesbioscience.com/journals/prion/03-Prion6-2-Transmission-and-strains.pdf White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection
Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS
Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. Previous experiments demonstrated that white-tailed deer are susceptible to sheep-derived scrapie by intracranial inoculation. The purpose of this study was to determine susceptibility of white-tailed deer to scrapie after a natural route of exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal (1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep clinically affected with scrapie. Non-inoculated deer were maintained as negative controls. All deer were observed daily for clinical signs. Deer were euthanized and necropsied when neurologic disease was evident, and tissues were examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and western blot (WB). One animal was euthanized 15 months post-inoculation (MPI) due to an injury. At that time, examination of obex and lymphoid tissues by IHC was positive, but WB of obex and colliculus were negative. Remaining deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by potential natural routes of inoculation. In-depth analysis of tissues will be done to determine similarities between scrapie in deer after intracranial and oral/intranasal inoculation and chronic wasting disease resulting from similar routes of inoculation.
see full text ;
www.usaha.org/Portals/6/Reports/2010/report-cwal-2010.pdf Envt.11: Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation
Justin Greenlee,† Robert Kunkle and Jodi Smith National Animal Disease Center, ARS, USDA; Ames, IA USA †Presenting author; Email: justin.greenlee@ars.usda.gov
Transmissible spongiform encephalopathies (TSEs, prion diseases) are chronic neurodegenerative diseases that occur in humans, cattle, sheep, goats, cervids and a number of laboratory animal models. There is no evidence of the natural occurrence of any form of TSE in the pig, but pigs have been shown to be susceptible to Bovine Spongiform Encephalopathy (BSE) infection by multiple-route parenteral challenge. However, pigs orally exposed at eight weeks of age to large amounts of brain from cattle clinically affected with BSE did not support infection after seven years of observation. In the US, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine, mink and poultry still occurs. Although unlikely, the potential for swine to have access to TSE-contaminated feedstuffs exists. The potential for swine to serve as a host for the agent of chronic wasting disease (CWD) is unknown. The purpose of this study was to perform intracerebral inoculation of the CWD agent to determine the potential of swine as a host for the CWD agent and their clinical susceptibility. This study utilized 26 swine randomly divided into controls (n = 6) and intracranial inoculates (n = 20). CWD inoculum was a pooled 10% (w/v) homogenate derived from three white-tailed deer clinically ill with CWD from three different sources (elk, white-tailed deer, mule deer) and was given by a single intracranial injection of 0.75 ml. Necropsies were done on ten animals at six months post inoculation (PI), at approximately the time the pigs were expected to reach market weight. Additional pigs have been necropsied due to intercurrent disease (primarily lameness) over the course of the study (29–64 months). Samples collected at necropsy were examined for spongiform change after routine staining (hematoxylin and eosin) and for immunoreactivity to prion protein (PrPSc) by immunohistochemistry. Further, brain samples from at least two regions were tested by western blot. No results suggestive of spongiform encephalopathy were obtained from animals necropsied at six months PI, but positive results after an incubation period of only six months would be uncharacteristic. A single animal was positive for CWD by IHC and WB at 64 months PI. Two inoculated pigs and one control pig remain alive, so it is not possible to determine the attack rate of CWD in swine at this time. However, lack of positive results in pigs necropsied at 29–56 months PI and the long incubation of the single positive case suggest that swine are unlikely to be affected by CWD if inoculated by a natural route.
www.landesbioscience.com/journals/prion/Prion5-Supp-PrionEnvironment.pdf?nocache=217787672 PO-041: Susceptibility of domestic cats to CWD infection
Amy Nalls, Jeanette Hayes-Klug, Kelly Anderson, Davis Seelig, Kevin Carnes, Susan Kraft, Edward Hoover, Candace Mathiason
Colorado State University; Fort Collins, CO USA
Domestic and non-domestic cats have been shown to be susceptible to feline spongiform encephalopathy (FSE); very likely due to consumption of bovine spongiform encephalopathy (BSE) contaminated meat. Because domestic and free-ranging nondomestic felids scavenge cervid carcasses, including those in areas affected by chronic wasting disease (CWD), we evaluated the susceptibility of domestic cats to CWD infection experimentally. Groups of n = 5 cats each were inoculated either intracerebrally (IC) or orally (PO) with CWD-infected deer brain homogenate.
Between 40 and 43 months two IC-inoculated cats developed slowly progressive symptoms including weight loss, anorexia, polydipsia, patterned motor behaviors, and ataxia”’ultimately mandating euthanasia. PrPCWD was detected in the brains of these animals by western blot, immunohistochemistry (IHC), and quaking-induced conversion (RT-QuIC) assays. No clinical signs of TSE were detected in the remaining primary passage cats at 86 months pi. Feline-adapted CWD (FelCWD) was sub-passaged into groups (n = 4 or 5) of cats by IC, PO, and IP/SQ routes.
All 5 IC inoculated cats developed symptoms of disease 20–24 months pi (approximately half the incubation period of primary passage). Additional symptoms in these animals included increasing aggressiveness and hyper responsiveness. FelCWD was demonstrated in the brains of all the affected cats by western blot and IHC. Currently, 3 of 4 IP/SQ, and 1 of 4 PO inoculated cats have developed abnormal behavior patterns consistent with the early stage of feline CWD. Magnetic resonance imaging (MRI) has been performed on 11 cats (6 clinically ill, 2 asymptomatic, and 3 age-matched negative controls). Abnormalities were detected in 4 of 6 clinically ill cats and included multifocal signal changes consistent with inflammation, ventricular size increases, more prominent sulci, and white matter tract cavitation.
These results demonstrate that CWD can be transmitted and adapted to the domestic cat, and raise the potential for cervid-to-feline transmission in nature.
PO-055: Transgenetic modeling of the CWD species barrier to humans
Eri Saijo,1 Sehun Kim,2 Claudio Soto,3 Glenn Telling2 1University of Kentucky College of Medicine; Fort Collins, CO USA; 2Department of Microbiology, Immunology and Pathology; Colorado State University; Fort Collins, CO USA ; 3Department of Neurology; University of Texas Houston Medical School; Houston, TX USA
Our recent studies raise significant concerns about the zoonotic potential of CWD. First, we showed that tissues consumed by humans derived from deer or elk with CWD, including skeletal muscle and antler velvet, harbor infectious prions. In other studies, cervid PrPSc converted human PrPC after CWD prions were stabilized by successive passages in vitro or in vivo.
We also identified at least two distinct strains of CWD, referred to as CWD1 and CWD2, the host-range properties of which are currently undefined. Other studies showed that codon 129, and the corresponding 132 residue in elk, significantly influenced the transmission of BSE and CWD prions respectively in transgenic (Tg) mouse models.
We inoculated Tg mice expressing human PrP encoding either methionine (M) or valine (V) at codon 129 with deer or elk CWD prions that previously produced disease in Tg mice expressing deer PrP with characteristics typical of CWD1 and CWD2 strains, as well as CWD prions that had been passaged multiple times in Tg mice expressing deer PrP.
While most Tg mice remained free of signs of prion disease for >260 days, small numbers of inoculated mice developed multiple, progressive neurological signs, that were consistent with prion disease. However, examination of brain materials from diseased mice failed to confirm the presence of protease-resistant human PrP. These preliminary results are consistent with a significant species barrier in humans to these CWD strains, and indicate that the 129 polymorphism does not modulate susceptibility.
PO-056: PrPCWD profiling of white-tailed deer (Odocoileus virginianus) with different Prnp genotypes following experimental oral infection
Camilo Duque Velasquez,1 Allen Herbst,1 Chad Johnson,2 Judd Aiken,1 Debbie McKenzie1 1Centre for Prions and Protein Folding Diseases; University of Alberta; Edmonton, AB Canada; 2Department of Soil Science; University of Wisconsin; Madison, WI USA
Chronic wasting disease (CWD) affects captive and free-ranging cervid populations in North America and farmed cervids of South Korea. CWD and scrapie are the only prion diseases in which the transmission occurs horizontally. The cervid Prnp gene is polymorphic at various positions. The effect of these changes on infection is influenced by the sequence and structure compatibility between the host and the infectious source. Prion strains have been described virtually in every prion disease and strongly impact disease characteristics (clinical symptoms, neuropathological profiles, incubation periods, species tropism as well as biochemical and biophysical properties of the abnormally folded prion protein). Prion protein sequence differences can result, upon subsequent infection, in the generation of novel strains as documented in sheep scrapie. We have previously shown that Prnp polymorphisms influence susceptibility to CWD in free-ranging white-tailed deer. In CWD-positive deer populations, alleles Q95G96 (wt) were over-represented compared to the H95G96 and Q95S96 alleles. Experimental oral infection of white-tailed deer with known Prnp genotypes (with inoculum from CWDpositive wt/wt deer) confirmed the link between prion protein primary sequence and the progression of disease. Heterozygous interference occurred in varying degrees as evidenced by the difference in the extension of the incubation period as an effect of alleles Q95S96 and H95G96. Interestingly, the biochemical profiles of the wt/Q95S96 and wt/H95G96 isolates resemble the wt/wt, differing only in the amount of protease resistant PrPCWD present suggesting that the wt allele is preferentially converted. PrPCWD profiling revealed differences between deer with at least one wt allele and the H95G96/Q95S96 deer suggesting that this PrPCWD is unique compared to the PrPCWD from wt/wt animals.
PO-057: Host factors influence prion strain adaptation
Crystal Meyerett Reid, Mark Zabel Colorado State University; Fort Collins, CO USA
Background. Chronic Wasting disease (CWD) is one of many prion-mediated diseases known as transmissible spongiform encephalopathies (TSEs). There is ever-increasing biological and biochemical evidence that prion pathogenesis is caused by the conversion of the normal host protein (PrPC) into an abnormal disease causing conformation (PrPRES). How prions encipher heritable strain properties without nucleic acid remains unclear. Previously we have shown that host factors have contributed to the adaptation of an original deer CWD prion strain to transgenic mice.
Materials and Methods. We assessed strain differences using biological and biochemical assays and found that amplified cervid prions and serial-passaged cervid prions were significantly different than that of the original cervid strain. It is possible that prion mutation and adaptation can broaden the host range. Previous reports, however, indicate that there is a strict species barrier preventing CWD infection in wildtype mice.
Results. Here we show the generation of a mouse-adapted strain of CWD upon serial passage into transgenic cervidized mice and then subsequent passage into wildtype mice. All wildtype mice remained non-clinical upon first passage but became completely susceptible after second passage with similar incubation times to those of mice terminally ill from a mouse adapted scrapie strain. Inoculation of our mouse adapted CWD strain back into cervidized mice delayed progression to terminal disease.
Conclusion. We conclude that prion strain adaptation and mutation is highly dependent upon host factors and host encoded PrPC primary sequence. Upon serial passage the adapted prion strain shares more characteristics with prion strains from the new host rather than the original species.
www.landesbioscience.com/journals/prion/03-Prion6-2-Transmission-and-strains.pdf OR-12: Chronic wasting disease transmission and pathogenesis in cervid and non-cervid Species
Edward A. Hoover, Candace K. Mathiason, Nicholas J. Haley, Timothy D. Kurt, Davis M. Seelig, Nathaniel D. Denkers, Amy V. Nalls, Mark D. Zabel, and Glenn C. Telling
Prion Research Program, Department of Microbiology, Immunology, and Pathology; Colorado State University; Fort Collins, CO USA
Since its recognition as a TSE in the late 1970s, chronic wasting disease (CWD) of cervids has been distinguished by its facile spread and is now recognized in 18 states, 2 Canadian provinces, and South Korea. The efficient horizontal spread of CWD reflects a prion/host relationship that facilitates efficient mucosal uptake, peripheral lymphoid amplification, and dissemination by exploiting excretory tissues and their products, helping to establish indirect/environmental and well as direct (e.g., salivary) transmission. Recent studies from our group also support the likelihood of early life mother to offspring and aerosol CWD prion transmission. Studies of cervid CWD exposure by natural routes indicate that incubation period for detection of overt infection, while still uncertain, may be much longer than originally thought.
Several non-cervid species can be infected by CWD experimentally (e.g., ferrets, voles, cats) with consequent species-specific disease phenotypes. The species-adapted prions so generated can be transmitted by mucosal, i.e., more natural, routes. Whether non-cervid species sympatric with deer/elk can be infected in nature, however, remains unknown. In vitro CWD prion amplification studies, in particular sPMCA, can foreshadow in vivo susceptibility and suggest the importance of the PrPC rigid loop region in species barrier permissiveness. Trans-species CWD amplification appears to broaden the host range/strain characteristics of the resultant prions. The origins of CWD remain unknown, however, the existence of multiple CWD prion strains/ quasi-species, the mechanisms of prion shedding/dissemination, and the relationship between sheep scrapie and CWD merit further investigation.
www.landesbioscience.com/journals/prion/01-Prion6-2-OralPresentations.pdf domestic cats and big cats
PO-081: Chronic wasting disease in the cat— Similarities to feline spongiform encephalopathy (FSE)
www.landesbioscience.com/journals/prion/04-Prion6-2-Pathogenesis-and-pathology.pdf chronic-wasting-disease.blogspot.com/2012/05/chronic-wasting-disease-cwd-prion2012.html www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf felinespongiformencephalopathyfse.blogspot.com/2011/08/susceptibility-of-domestic-cats-to-cwd.html PO-081: Chronic wasting disease in the cat— Similarities to feline spongiform encephalopathy (FSE)
www.landesbioscience.com/journals/prion/04-Prion6-2-Pathogenesis-and-pathology.pdf chronic-wasting-disease.blogspot.com/2012/05/chronic-wasting-disease-cwd-prion2012.html Thursday, May 31, 2012
CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission, Scrapie, cats, species barrier, burial, and more
chronic-wasting-disease.blogspot.com/2012/05/chronic-wasting-disease-cwd-prion2012.html ----- Original Message -----
From: David Colby To: flounder9@verizon.net
Cc: stanley@XXXXXXXX
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, PhD
Assistant Professor Department of Chemical Engineering University of Delaware
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SNIP...SEE FULL TEXT ;
betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html sorry for my long winded post, but thought some might be interested in this science.........
kind regards,
terry
