flounder9
Member
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research Unit
2011 Annual Report
1a.Objectives (from AD-416) Obj. 1. Assess the cross species transmissibility of transmissible spongiform encephalopathies (TSEs) in livestock and wildlife. Obj. 2. Investigate the pathobiology of TSEs in natural and secondary hosts. Obj. 3. Investigate pathogenesis and ante mortem detection of bovine spongiform encephalopathy (BSE). Obj. 4. Develop a method to detect central nervous system (CNS) tissue contamination on carcasses. Obj. 5. Discover effective methods to inactivate TSE agents in agricultural settings.
1b.Approach (from AD-416) Studies are focused on the four animal Transmissible Spongiform Encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; and transmissible mink encephalopathy (TME). These agents will be tested for cross-species transmissibility into various livestock and cervid species using both oral and intracerebral inoculation. Sites of accumulation, routes of infection, methods of isolate differentiation, and in the case of BSE, genetics of susceptibility and ante-mortem diagnostics, will be investigated. Existing technology developed at the National Animal Disease Center and those used in the meat packing industry for the detection of fecal contamination on carcasses will be adapted to detect CNS tissue contamination on carcasses. Methods of TSE inactivation will be evaluated for efficacy in agricultural settings.
3.Progress Report This is the final report for project 3625-32000-086-00D, terminated in September 2011 and replaced by 3625-32000-103-00D. The project plan involved 5 objectives.
In Objective 1, Assess cross-species transmissibility of transmissible spongiform encephalopathies (TSEs) in livestock and wildlife, numerous experiments assessing the susceptibility of various TSEs in different host species were conducted. Most notable is deer inoculated with scrapie, which exhibits similarities to chronic wasting disease (CWD) in deer suggestive of sheep scrapie as an origin of CWD.
In Objective 2, Investigate the pathobiology of TSEs in natural and secondary hosts, deer were inoculated with CWD-infected blood. Several animals developed clinical signs, a result consistent with CWD infectivity in blood. Also, biochemical strain typing commonly used for rodent models of TSE was investigated to assess the importance of genetic variability in natural hosts and how to apply these methods to natural hosts.
Objective 3, Investigate pathogenesis and antemortem detection of bovine spongiform encephalopathy (BSE), involves several different research areas. Our results in genetic susceptibility of BSE support the now widely accepted conclusion that atypical BSE is a spontaneous TSE in cattle. This has important implications for the ruminant feed ban, food safety, and our understanding of the origins of BSE. Also as part of Obj. 3, we identified the first recognized case of genetic BSE where a natural case of BSE was identified in an animal containing a polymorphism analogous to a human polymorphism that causes a genetic TSE. Bovine spongiform encephalopathy has long been believed to only be a feed-borne disease. Together, our results show for the first time the presence of three different etiologies for BSE as are known to occur in humans. As part of our investigation, classical, and atypical BSE isolates were inoculated into cattle. Upon completion, this work will represent the first thorough comparison of domestic and international BSE isolates, including both classical and atypical BSE. An antemortem diagnostic technique based upon retinal function was developed and is routinely applied to experimental animals on site. This technique detects a TSE before the onset of clinical signs. Work is ongoing to increase the number of animals containing the E211K polymorphism, a potential cause of genetic BSE; this will provide the only means by which to prove the novel allele may cause BSE. The unusual E211K BSE material has also been successfully amplified in one of these animals.
Objective 4, Develop a method to detect CNS tissue contamination on carcasses, resulted in a successful method that may be applied through adaptation of existing technology currently used to detect fecal contamination on carcasses.
In Objective 5, Determine effective methods to inactivate TSE agents in agricultural settings, compounds applicable to agricultural settings were evaluated; the results are being prepared for publication. As part of this objective, a natural host model for assessing inactivation was developed. Despite experimental success the model is not suitable due to incubation time.
4.Accomplishments 1. Deer inoculated with domestic isolates of sheep scrapie. Scrapie-affected deer exhibit 2 different patterns of disease associated prion protein. In some regions of the brain the pattern is much like that observed for scrapie, while in others it is more like chronic wasting disease (CWD), the transmissible spongiform encephalopathy typically associated with deer. This work conducted by ARS scientists at the National Animal Disease Center, Ames, IA suggests that an interspecies transmission of sheep scrapie to deer may have been the origin of CWD. This is important for husbandry practices with both captive deer, elk and sheep for farmers and ranchers attempting to keep their herds and flocks free of CWD and scrapie.
2. Demonstrated transmissibility of K211 BSE, a rare genetic form of bovine spongiform encephalopathy (BSE), to cattle. Cattle containing the rare K211 PRNP gene have been produced in-house and used in this study conducted by ARS scientists at the National Animal Disease Center, Ames, IA. These animals have been inoculated with both K211 BSE and classical BSE. The K211 BSE is transmissible and progresses far more rapidly in K211 cattle than does classical BSE. Because of their genetic susceptibility to BSE, K211 PRNP cattle have a very rapid incubation time and may be more susceptible to TSEs, which are two characteristics that make them highly desirable for future studies of antemortem diagnostics and residual infectivity or risk materials after decontamination. The possibility remains that K211 BSE transmitted to conventional cattle will result in a disease phenotype similar to classical BSE. If this turns out to be true, then it will be very important in that it suggests a very rare genetic form of BSE could have been the original source of brain material responsible for the U.K. BSE epidemic. Current human and animal feed bans regarding specified risk materials from cattle protect humans and animals from a recurrence of such an epidemic.
Review Publications Hamir, A.N., Greenlee, J.J., Stanton, T.B., Smith, J.D., Doucette, S., Kunkle, R.A., Stasko, J.A., Richt, J.A., Kehrli, Jr., M.E. 2011. Experimental inoculation of raccoons (Procyon lotor) with Spiroplasma mirum and transmissible mink encephalopathy (TME). Canadian Journal of Veterinary Research. 75(1):18–24.
Hamir, A.N., Greenlee, J.J., Nicholson, E.M., Kunkle, R.A., Richt, J.A., Miller, J.M., Hall, M. 2011. Experimental transmission of chronic wasting disease (CWD) from elk and white-tailed deer to fallow deer by intracerebral route: final report. Canadian Journal of Veterinary Research. 75(2):152-156.
Smith, J.D., Hamir, A.N., Greenlee, J.J. 2011. Cartilaginous metaplasia in the sclera of Suffolk sheep. Veterinary Pathology. 48(4):827-829.
Loiacono, C.M., Beckwith, N., Kunkle, R.A., Orcutt, D., Hall, S.M. 2010. Detection of PrPSc in formalin-fixed, paraffin embedded tissue by Western blot differentiates classical scrapie, Nor98 scrapie, and bovine spongiform encephalopathy. Journal of Veterinary Diagnostic Investigation. 22(5):684-689.
Hamir, A.N., Kehrli, Jr., M.E., Kunkle, R.A., Greenlee, J.J., Nicholson, E.M., Richt, J.A., Miller, J.M., Cutlip, R.C. 2011. Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle. Journal of Veterinary Diagnostic Investigation. 23(3):407-420.
Nicholson, E.M. 2011. Enrichment of PrPSc in formalin-fixed, paraffin-embedded tissues prior to analysis by Western blot. Journal of Veterinary Diagnostic Investigation. 23(4):790-792.
http://ars.usda.gov/research/projects/projects.htm?ACCN_NO=411467&showpars=true&fy=2011
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
http://collections.europarchive.org...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.
http://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 ;
http://www.usaha.org/Portals/6/Reports/2010/report-cwal-2010.pdf
Envt.06:
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Aru Balachandran,2 Jürgen Richt,3 Vincent Beringue,4 Juan-Maria Torres,5 Paul Brown,1 Bob Hills6 and Jean-Philippe Deslys1
1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Canadian Food Inspection Agency; Ottawa, ON Canada; 3Kansas State University; Manhattan, KS USA; 4INRA; Jouy-en-Josas, France; 5INIA; Madrid, Spain; 6Health Canada; Ottawa, ON Canada
†Presenting author; Email: emmanuel.comoy@cea.fr
The constant increase of chronic wasting disease (CWD) incidence in North America raises a question about their zoonotic potential. A recent publication showed their transmissibility to new-world monkeys, but no transmission to old-world monkeys, which are phylogenetically closer to humans, has so far been reported. Moreover, several studies have failed to transmit CWD to transgenic mice overexpressing human PrP. Bovine spongiform encephalopathy (BSE) is the only animal prion disease for which a zoonotic potential has been proven. We described the transmission of the atypical BSE-L strain of BSE to cynomolgus monkeys, suggesting a weak cattle-to-primate species barrier. We observed the same phenomenon with a cattleadapted strain of TME (Transmissible Mink Encephalopathy). Since cattle experimentally exposed to CWD strains have also developed spongiform encephalopathies, we inoculated brain tissue from CWD-infected cattle to three cynomolgus macaques as well as to transgenic mice overexpressing bovine or human PrP. Since CWD prion strains are highly lymphotropic, suggesting an adaptation of these agents after peripheral exposure, a parallel set of four monkeys was inoculated with CWD-infected cervid brains using the oral route. Nearly four years post-exposure, monkeys exposed to CWD-related prion strains remain asymptomatic. In contrast, bovinized and humanized transgenic mice showed signs of infection, suggesting that CWD-related prion strains may be capable of crossing the cattle-to-primate species barrier. Comparisons with transmission results and incubation periods obtained after exposure to other cattle prion strains (c-BSE, BSE-L, BSE-H and cattle-adapted TME) will also be presented, in order to evaluate the respective risks of each strain.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease
Martin L. Daus,1,† Johanna Breyer,2 Katjs Wagenfuehr,1 Wiebke Wemheuer,2 Achim Thomzig,1 Walter Schulz-Schaeffer2 and Michael Beekes1 1Robert Koch Institut; P24 TSE; Berlin, Germany; 2Department of Neuropathology, Prion and Dementia Research Unit, University Medical Center Göttingen; Göttingen, Germany
†Presenting author; Email: dausm@rki.de
Chronic wasting disease (CWD) is a contagious, rapidly spreading transmissible spongiform encephalopathy (TSE) occurring in cervids in North America. Despite efficient horizontal transmission of CWD among cervids natural transmission of the disease to other species has not yet been observed. Here, we report a direct biochemical demonstration of pathological prion protein PrPTSE and of PrPTSE-associated seeding activity in skeletal muscles of CWD-infected cervids. The presence of PrPTSE was detected by Western- and postfixed frozen tissue blotting, while the seeding activity of PrPTSE was revealed by protein misfolding cyclic amplification (PMCA). The concentration of PrPTSE in skeletal muscles of CWD-infected WTD was estimated to be approximately 2000- to 10000-fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE was located in muscle- associated nerve fascicles but not, in detectable amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.
http://www.landesbioscience.com/journals/prion/Prion5-Supp-PrionEnvironment.pdf?nocache=1333529975
Sunday, January 22, 2012
Chronic Wasting Disease CWD cervids interspecies transmission
http://chronic-wasting-disease.blogspot.com/2012/01/chronic-wasting-disease-cwd-cervids.html
for those interested, see more here ;
Saturday, October 6, 2012
TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES 2011 Annual Report
http://transmissiblespongiformencep...2012/10/transmission-differentiation-and.html
kind regards,
terry
2011 Annual Report
1a.Objectives (from AD-416) Obj. 1. Assess the cross species transmissibility of transmissible spongiform encephalopathies (TSEs) in livestock and wildlife. Obj. 2. Investigate the pathobiology of TSEs in natural and secondary hosts. Obj. 3. Investigate pathogenesis and ante mortem detection of bovine spongiform encephalopathy (BSE). Obj. 4. Develop a method to detect central nervous system (CNS) tissue contamination on carcasses. Obj. 5. Discover effective methods to inactivate TSE agents in agricultural settings.
1b.Approach (from AD-416) Studies are focused on the four animal Transmissible Spongiform Encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; and transmissible mink encephalopathy (TME). These agents will be tested for cross-species transmissibility into various livestock and cervid species using both oral and intracerebral inoculation. Sites of accumulation, routes of infection, methods of isolate differentiation, and in the case of BSE, genetics of susceptibility and ante-mortem diagnostics, will be investigated. Existing technology developed at the National Animal Disease Center and those used in the meat packing industry for the detection of fecal contamination on carcasses will be adapted to detect CNS tissue contamination on carcasses. Methods of TSE inactivation will be evaluated for efficacy in agricultural settings.
3.Progress Report This is the final report for project 3625-32000-086-00D, terminated in September 2011 and replaced by 3625-32000-103-00D. The project plan involved 5 objectives.
In Objective 1, Assess cross-species transmissibility of transmissible spongiform encephalopathies (TSEs) in livestock and wildlife, numerous experiments assessing the susceptibility of various TSEs in different host species were conducted. Most notable is deer inoculated with scrapie, which exhibits similarities to chronic wasting disease (CWD) in deer suggestive of sheep scrapie as an origin of CWD.
In Objective 2, Investigate the pathobiology of TSEs in natural and secondary hosts, deer were inoculated with CWD-infected blood. Several animals developed clinical signs, a result consistent with CWD infectivity in blood. Also, biochemical strain typing commonly used for rodent models of TSE was investigated to assess the importance of genetic variability in natural hosts and how to apply these methods to natural hosts.
Objective 3, Investigate pathogenesis and antemortem detection of bovine spongiform encephalopathy (BSE), involves several different research areas. Our results in genetic susceptibility of BSE support the now widely accepted conclusion that atypical BSE is a spontaneous TSE in cattle. This has important implications for the ruminant feed ban, food safety, and our understanding of the origins of BSE. Also as part of Obj. 3, we identified the first recognized case of genetic BSE where a natural case of BSE was identified in an animal containing a polymorphism analogous to a human polymorphism that causes a genetic TSE. Bovine spongiform encephalopathy has long been believed to only be a feed-borne disease. Together, our results show for the first time the presence of three different etiologies for BSE as are known to occur in humans. As part of our investigation, classical, and atypical BSE isolates were inoculated into cattle. Upon completion, this work will represent the first thorough comparison of domestic and international BSE isolates, including both classical and atypical BSE. An antemortem diagnostic technique based upon retinal function was developed and is routinely applied to experimental animals on site. This technique detects a TSE before the onset of clinical signs. Work is ongoing to increase the number of animals containing the E211K polymorphism, a potential cause of genetic BSE; this will provide the only means by which to prove the novel allele may cause BSE. The unusual E211K BSE material has also been successfully amplified in one of these animals.
Objective 4, Develop a method to detect CNS tissue contamination on carcasses, resulted in a successful method that may be applied through adaptation of existing technology currently used to detect fecal contamination on carcasses.
In Objective 5, Determine effective methods to inactivate TSE agents in agricultural settings, compounds applicable to agricultural settings were evaluated; the results are being prepared for publication. As part of this objective, a natural host model for assessing inactivation was developed. Despite experimental success the model is not suitable due to incubation time.
4.Accomplishments 1. Deer inoculated with domestic isolates of sheep scrapie. Scrapie-affected deer exhibit 2 different patterns of disease associated prion protein. In some regions of the brain the pattern is much like that observed for scrapie, while in others it is more like chronic wasting disease (CWD), the transmissible spongiform encephalopathy typically associated with deer. This work conducted by ARS scientists at the National Animal Disease Center, Ames, IA suggests that an interspecies transmission of sheep scrapie to deer may have been the origin of CWD. This is important for husbandry practices with both captive deer, elk and sheep for farmers and ranchers attempting to keep their herds and flocks free of CWD and scrapie.
2. Demonstrated transmissibility of K211 BSE, a rare genetic form of bovine spongiform encephalopathy (BSE), to cattle. Cattle containing the rare K211 PRNP gene have been produced in-house and used in this study conducted by ARS scientists at the National Animal Disease Center, Ames, IA. These animals have been inoculated with both K211 BSE and classical BSE. The K211 BSE is transmissible and progresses far more rapidly in K211 cattle than does classical BSE. Because of their genetic susceptibility to BSE, K211 PRNP cattle have a very rapid incubation time and may be more susceptible to TSEs, which are two characteristics that make them highly desirable for future studies of antemortem diagnostics and residual infectivity or risk materials after decontamination. The possibility remains that K211 BSE transmitted to conventional cattle will result in a disease phenotype similar to classical BSE. If this turns out to be true, then it will be very important in that it suggests a very rare genetic form of BSE could have been the original source of brain material responsible for the U.K. BSE epidemic. Current human and animal feed bans regarding specified risk materials from cattle protect humans and animals from a recurrence of such an epidemic.
Review Publications Hamir, A.N., Greenlee, J.J., Stanton, T.B., Smith, J.D., Doucette, S., Kunkle, R.A., Stasko, J.A., Richt, J.A., Kehrli, Jr., M.E. 2011. Experimental inoculation of raccoons (Procyon lotor) with Spiroplasma mirum and transmissible mink encephalopathy (TME). Canadian Journal of Veterinary Research. 75(1):18–24.
Hamir, A.N., Greenlee, J.J., Nicholson, E.M., Kunkle, R.A., Richt, J.A., Miller, J.M., Hall, M. 2011. Experimental transmission of chronic wasting disease (CWD) from elk and white-tailed deer to fallow deer by intracerebral route: final report. Canadian Journal of Veterinary Research. 75(2):152-156.
Smith, J.D., Hamir, A.N., Greenlee, J.J. 2011. Cartilaginous metaplasia in the sclera of Suffolk sheep. Veterinary Pathology. 48(4):827-829.
Loiacono, C.M., Beckwith, N., Kunkle, R.A., Orcutt, D., Hall, S.M. 2010. Detection of PrPSc in formalin-fixed, paraffin embedded tissue by Western blot differentiates classical scrapie, Nor98 scrapie, and bovine spongiform encephalopathy. Journal of Veterinary Diagnostic Investigation. 22(5):684-689.
Hamir, A.N., Kehrli, Jr., M.E., Kunkle, R.A., Greenlee, J.J., Nicholson, E.M., Richt, J.A., Miller, J.M., Cutlip, R.C. 2011. Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle. Journal of Veterinary Diagnostic Investigation. 23(3):407-420.
Nicholson, E.M. 2011. Enrichment of PrPSc in formalin-fixed, paraffin-embedded tissues prior to analysis by Western blot. Journal of Veterinary Diagnostic Investigation. 23(4):790-792.
http://ars.usda.gov/research/projects/projects.htm?ACCN_NO=411467&showpars=true&fy=2011
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
http://collections.europarchive.org...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.
http://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 ;
http://www.usaha.org/Portals/6/Reports/2010/report-cwal-2010.pdf
Envt.06:
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Aru Balachandran,2 Jürgen Richt,3 Vincent Beringue,4 Juan-Maria Torres,5 Paul Brown,1 Bob Hills6 and Jean-Philippe Deslys1
1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Canadian Food Inspection Agency; Ottawa, ON Canada; 3Kansas State University; Manhattan, KS USA; 4INRA; Jouy-en-Josas, France; 5INIA; Madrid, Spain; 6Health Canada; Ottawa, ON Canada
†Presenting author; Email: emmanuel.comoy@cea.fr
The constant increase of chronic wasting disease (CWD) incidence in North America raises a question about their zoonotic potential. A recent publication showed their transmissibility to new-world monkeys, but no transmission to old-world monkeys, which are phylogenetically closer to humans, has so far been reported. Moreover, several studies have failed to transmit CWD to transgenic mice overexpressing human PrP. Bovine spongiform encephalopathy (BSE) is the only animal prion disease for which a zoonotic potential has been proven. We described the transmission of the atypical BSE-L strain of BSE to cynomolgus monkeys, suggesting a weak cattle-to-primate species barrier. We observed the same phenomenon with a cattleadapted strain of TME (Transmissible Mink Encephalopathy). Since cattle experimentally exposed to CWD strains have also developed spongiform encephalopathies, we inoculated brain tissue from CWD-infected cattle to three cynomolgus macaques as well as to transgenic mice overexpressing bovine or human PrP. Since CWD prion strains are highly lymphotropic, suggesting an adaptation of these agents after peripheral exposure, a parallel set of four monkeys was inoculated with CWD-infected cervid brains using the oral route. Nearly four years post-exposure, monkeys exposed to CWD-related prion strains remain asymptomatic. In contrast, bovinized and humanized transgenic mice showed signs of infection, suggesting that CWD-related prion strains may be capable of crossing the cattle-to-primate species barrier. Comparisons with transmission results and incubation periods obtained after exposure to other cattle prion strains (c-BSE, BSE-L, BSE-H and cattle-adapted TME) will also be presented, in order to evaluate the respective risks of each strain.
Envt.07:
Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease
Martin L. Daus,1,† Johanna Breyer,2 Katjs Wagenfuehr,1 Wiebke Wemheuer,2 Achim Thomzig,1 Walter Schulz-Schaeffer2 and Michael Beekes1 1Robert Koch Institut; P24 TSE; Berlin, Germany; 2Department of Neuropathology, Prion and Dementia Research Unit, University Medical Center Göttingen; Göttingen, Germany
†Presenting author; Email: dausm@rki.de
Chronic wasting disease (CWD) is a contagious, rapidly spreading transmissible spongiform encephalopathy (TSE) occurring in cervids in North America. Despite efficient horizontal transmission of CWD among cervids natural transmission of the disease to other species has not yet been observed. Here, we report a direct biochemical demonstration of pathological prion protein PrPTSE and of PrPTSE-associated seeding activity in skeletal muscles of CWD-infected cervids. The presence of PrPTSE was detected by Western- and postfixed frozen tissue blotting, while the seeding activity of PrPTSE was revealed by protein misfolding cyclic amplification (PMCA). The concentration of PrPTSE in skeletal muscles of CWD-infected WTD was estimated to be approximately 2000- to 10000-fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE was located in muscle- associated nerve fascicles but not, in detectable amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.
http://www.landesbioscience.com/journals/prion/Prion5-Supp-PrionEnvironment.pdf?nocache=1333529975
Sunday, January 22, 2012
Chronic Wasting Disease CWD cervids interspecies transmission
http://chronic-wasting-disease.blogspot.com/2012/01/chronic-wasting-disease-cwd-cervids.html
for those interested, see more here ;
Saturday, October 6, 2012
TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES 2011 Annual Report
http://transmissiblespongiformencep...2012/10/transmission-differentiation-and.html
kind regards,
terry
