scholarly journals Preclinical diagnosis of chronic wasting disease in captive mule deer (Odocoileus hemionus) and white-tailed deer (Odocoileus virginianus) using tonsillar biopsy

2002 ◽  
Vol 83 (10) ◽  
pp. 2629-2634 ◽  
Author(s):  
Margaret A. Wild ◽  
Terry R. Spraker ◽  
Christina J. Sigurdson ◽  
Katherine I. O’Rourke ◽  
Michael W. Miller
Keyword(s):  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathy ◽  
Mule Deer ◽  
Clinical Signs ◽  
Odocoileus Hemionus ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Protein Marker ◽  
Preclinical Diagnosis ◽  
Management Approaches

The usefulness of tonsillar biopsy on live deer for preclinical diagnosis of the transmissible spongiform encephalopathy chronic wasting disease (CWD) was evaluated. Disease was tracked in a CWD-endemic herd using serial tonsillar biopsies collected at 6 to 9 month intervals from 34 captive mule deer (Odocoileus hemionus) and five white-tailed deer (O. virginianus). Tonsillar biopsies were examined for accumulation of PrPCWD, the protein marker for infection, using immunohistochemical (IHC) staining. 26/34 (76%) mule deer and 4/5 (80%) white-tailed deer had PrPCWD accumulation in tonsillar biopsies; CWD was subsequently confirmed by post-mortem examination in all 30 of these tonsillar-positive deer. Six mule deer with IHC-negative tonsillar biopsies had positive brain and tonsillar IHC staining upon death 12 to 40 months following the last biopsy. PrPCWD accumulation in tonsillar biopsy was observed 2 to 20 months before CWD-related death and up to 14 months before onset of clinical signs of CWD. Tonsillar biopsies from 3-month-old mule deer (n=6) were IHC negative, but PrPCWD accumulation was detected in tonsillar biopsies from 7/10 mule deer by 19 months of age. Tonsillar biopsy evaluated with IHC staining is a useful technique for the preclinical diagnosis of CWD in live mule deer and white-tailed deer when intensive management approaches are possible.

scholarly journals Inhibition of Protease-Resistant Prion Protein Formation in a Transformed Deer Cell Line Infected with Chronic Wasting Disease

2006 ◽  
Vol 80 (2) ◽  
pp. 596-604 ◽  
Author(s):  
Gregory J. Raymond ◽  
Emily A. Olsen ◽  
Kil Sun Lee ◽  
Lynne D. Raymond ◽  
P. Kruger Bryant ◽  
...  
Keyword(s):  
Cell Line ◽  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathy ◽  
Mule Deer ◽  
Simian Virus 40 ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Neuronal Marker

ABSTRACT Chronic wasting disease (CWD) is an emerging transmissible spongiform encephalopathy (prion disease) of North American cervids, i.e., mule deer, white-tailed deer, and elk (wapiti). To facilitate in vitro studies of CWD, we have developed a transformed deer cell line that is persistently infected with CWD. Primary cultures derived from uninfected mule deer brain tissue were transformed by transfection with a plasmid containing the simian virus 40 genome. A transformed cell line (MDB) was exposed to microsomes prepared from the brainstem of a CWD-affected mule deer. CWD-associated, protease-resistant prion protein (PrPCWD) was used as an indicator of CWD infection. Although no PrPCWD was detected in any of these cultures after two passes, dilution cloning of cells yielded one PrPCWD-positive clone out of 51. This clone, designated MDBCWD, has maintained stable PrPCWD production through 32 serial passes thus far. A second round of dilution cloning yielded 20 PrPCWD-positive subclones out of 30, one of which was designated MDBCWD2. The MDBCWD2 cell line was positive for fibronectin and negative for microtubule-associated protein 2 (a neuronal marker) and glial fibrillary acidic protein (an activated astrocyte marker), consistent with derivation from brain fibroblasts (e.g., meningeal fibroblasts). Two inhibitors of rodent scrapie protease-resistant PrP accumulation, pentosan polysulfate and a porphyrin compound, indium (III) meso-tetra(4-sulfonatophenyl)porphine chloride, potently blocked PrPCWD accumulation in MDBCWD cells. This demonstrates the utility of these cells in a rapid in vitro screening assay for PrPCWD inhibitors and suggests that these compounds have potential to be active against CWD in vivo.

Rapid Procedure For Detecting Scrapie-Associated Fibrils In Chronic Wasting Disease Of Elk And Mule Deer

1999 ◽  
Vol 5 (S2) ◽  
pp. 1310-1311
Author(s):  
C.E. Hearne ◽  
J.L. Clapper ◽  
K.L. DeVries ◽  
E.S. Williams
Keyword(s):  
High Speed ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathy ◽  
Mule Deer ◽  
Proteinase K ◽  
Abnormal Behavior ◽  
Enzyme Treatment ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Gradual Loss

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of mule deer and elk. Affected animals are characterized clinically by a combination of abnormal behavior and gradual loss of body condition. The disease is invariably fatal. Diagnosis of CWD is made by histologic examination of the central nervous system and microscopic lesions of CWD are typical of the TSEs. Brains from CWD-suspect elk and mule deer can be examined by transmission electron microscopy (TEM) for the presence of scrapie-associated fibrils (SAF). Western blot methods identify abnormal prion protein (PrPres) which accumulates in the brains of animals with TSE, including CWD.Conventional SAF purification procedures for TEM examination of CWD-suspect brain tissue require both high speed and ultracentrifugation steps followed by Proteinase K enzyme treatment. Modifications used in this experiment include early Proteinase K, or Proteinase K and Collagenase treatment prior to high speed centrifugation and the elimination of the ultracentrifugation step.

scholarly journals Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus )

1999 ◽  
Vol 80 (10) ◽  
pp. 2757-2764 ◽  
Author(s):  
Christina J. Sigurdson ◽  
Elizabeth S. Williams ◽  
Michael W. Miller ◽  
Terry R. Spraker ◽  
Katherine I. O’Rourke ◽  
...  
Keyword(s):  
Lymph Node ◽  
Alimentary Tract ◽  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Odocoileus Hemionus ◽  
Oral Exposure ◽  
Spongiform Encephalopathy ◽  
Lymphoid Tissues ◽  
Acid Proteinase ◽  
Wasting Disease

Mule deer fawns (Odocoileus hemionus) were inoculated orally with a brain homogenate prepared from mule deer with naturally occurring chronic wasting disease (CWD), a prion-induced transmissible spongiform encephalopathy. Fawns were necropsied and examined for PrP res, the abnormal prion protein isoform, at 10, 42, 53, 77, 78 and 80 days post-inoculation (p.i.) using an immunohistochemistry assay modified to enhance sensitivity. PrPres was detected in alimentary-tract-associated lymphoid tissues (one or more of the following: retropharyngeal lymph node, tonsil, Peyer’s patch and ileocaecal lymph node) as early as 42 days p.i. and in all fawns examined thereafter (53 to 80 days p.i.). No PrPres staining was detected in lymphoid tissue of three control fawns receiving a control brain inoculum, nor was PrPres detectable in neural tissue of any fawn. PrPres-specific staining was markedly enhanced by sequential tissue treatment with formic acid, proteinase K and hydrated autoclaving prior to immunohistochemical staining with monoclonal antibody F89/160.1.5. These results indicate that CWD PrP res can be detected in lymphoid tissues draining the alimentary tract within a few weeks after oral exposure to infectious prions and may reflect the initial pathway of CWD infection in deer. The rapid infection of deer fawns following exposure by the most plausible natural route is consistent with the efficient horizontal transmission of CWD in nature and enables accelerated studies of transmission and pathogenesis in the native species.

Neuropathology of Chronic Wasting Disease of Mule Deer (Odocoileus hemionus) and Elk (Cervus elaphus nelsoni)

1993 ◽  
Vol 30 (1) ◽  
pp. 36-45 ◽  
Author(s):  
E. S. Williams ◽  
S. Young
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Cervus Elaphus ◽  
Chronic Wasting Disease ◽  
Neuronal Degeneration ◽  
Mule Deer ◽  
Amyloid Plaques ◽  
Odocoileus Hemionus ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Cervus Elaphus Nelsoni

The pathology of the central nervous system of nine mule deer ( Odocoileus hemionus) and six elk ( Cervus elaphus nelsoni) with chronic wasting disease, a spongiform encephalopathy of mule deer and elk, was studied by light microscopy. Lesions were similar in both species and were characterized by spongiform transformation of gray matter, intracytoplasmic vacuolation of neurons, neuronal degeneration and loss, astrocytic hypertrophy and hyperplasia, occurrence of amyloid plaques, and absence of significant inflammatory response. Distribution and severity of lesions were evaluated at 57 locations; there were only minor differences between deer and elk. Consistent, severe lesions occurred in olfactory tubercle and cortex, hypothalamus, and the parasympathetic vagal nucleus of deer, and sections examined from these regions would be sufficient to establish a diagnosis of chronic wasting disease. Lesions were milder in these locations in elk but were sufficiently apparent to be of diagnostic value. Other differences included increased severity of lesions in some thalamic nuclei in elk in contrast to deer, the occurrence of amyloid plaques demonstrable by hematoxylin and eosin and histochemical stains in deer in contrast to elk, and the presence of mild white matter lesions in elk but not in deer. Lesions of chronic wasting disease were qualitatively comparable to those of scrapie, bovine spongiform encephalopathy, transmissible mink encephalopathy, and the human spongiform encephalopathies. Topographic distribution and lesion severity of chronic wasting disease were most similar to those of scrapie and bovine spongiform encephalopathy. Duration of clinical disease did not significantly influence lesion distribution or severity in either species.

scholarly journals Abundant PrPCWD in Tonsil from Mule Deer with Preclinical Chronic Wasting Disease

2003 ◽  
Vol 15 (4) ◽  
pp. 320-323 ◽  
Author(s):  
Katherine I. O'Rourke ◽  
Dongyue Zhuang ◽  
Amy Lyda ◽  
Gabriel Gomez ◽  
Elizabeth S. Williams ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
High Throughput Screening ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathy ◽  
Mule Deer ◽  
Screening Tests ◽  
Spongiform Encephalopathy ◽  
Dot Blot ◽  
Wasting Disease ◽  
Dot Blot Assay

A monoclonal antibody dot-blot assay was used to evaluate detergent lysates of tonsil tissue from mule deer to detect PrPCWD, the marker for the cervid transmissible spongiform encephalopathy chronic wasting disease (CWD). Samples of formalin-fixed brain and tonsil tissues from mule deer were examined for PrPCWD using immunohistochemistry (IHC) with Mab F99/97.6.1, the gold standard for diagnosis of preclinical CWD. The contralateral tonsil from each of the 143 deer was prepared for confirmatory IHC and as a 10% (wt/vol) detergent lysate without purification or enrichment steps for monoclonal antibody dot-blot assay. PrPCWD was detected by dot-blot assay in 49 of 50 samples considered positive by IHC. Forty-eight of the positive samples were evaluated with a quantitative dot-blot assay calibrated with recombinant PrP. Tonsillar PrPCWD concentrations ranged from 34 to 1,188 ng per 0.5 mg starting wet weight of tissue. The abundant PrPCWD in mule deer tonsil will facilitate development and validation of high-throughput screening tests for CWD in large populations of free-ranging deer.

scholarly journals Patterns of PrPCWD accumulation during the course of chronic wasting disease infection in orally inoculated mule deer (Odocoileus hemionus)

2006 ◽  
Vol 87 (11) ◽  
pp. 3451-3461 ◽  
Author(s):  
Karen A. Fox ◽  
Jean E. Jewell ◽  
Elizabeth S. Williams ◽  
Michael W. Miller
Keyword(s):  
Time Course ◽  
Chronic Wasting Disease ◽  
Control Strategies ◽  
Mule Deer ◽  
Odocoileus Hemionus ◽  
Spongiform Encephalopathy ◽  
Lymphoid Tissues ◽  
Wasting Disease ◽  
Potential Control ◽  
Epidemic Dynamics

Patterns of abnormal prion protein (PrP) accumulation during the course of chronic wasting disease (CWD) infection were studied and the distribution and timing of disease-associated PrP (PrPCWD) deposition and lesions in 19 mule deer (Odocoileus hemionus) 90–785 days after oral inoculation were described. PrPCWD deposition occurred relatively rapidly and widely in lymphoid tissues, later in central and peripheral nervous tissues and sporadically in a variety of tissues and organs in terminal disease stages. Development of spongiform encephalopathy lagged behind PrPCWD deposition in the central nervous system (CNS), but occurred in the same neuroanatomical locations. PrPCWD deposition in the lymphatic and nervous systems tended to be consistent and progressive in specific organs and tissues. Locations of PrPCWD deposition were similar between deer of two PrP genotypes (225SS and 225SF), but the time course differed between genotypes: in 225SF deer, PrPCWD accumulated more slowly in lymphatic tissues than in 225SS animals, but that disparity was small in comparison to the disparity between genotypes in timing of deposition in CNS tissue. These data confirm retropharyngeal lymph node and medulla oblongata at the level of the obex as early sites of PrPCWD accumulation in mule deer with CWD. Data on the relative time frames for and genetic influences on PrPCWD accumulation may also offer insights about epidemic dynamics and potential control strategies.

Distribution of Protease-resistant Prion Protein and Spongiform Encephalopathy in Free-ranging Mule Deer (Odocoileus hemionus) with Chronic Wasting Disease

2002 ◽  
Vol 39 (5) ◽  
pp. 546-556 ◽  
Author(s):  
T. R. Spraker ◽  
R. R. Zink ◽  
B. A. Cummings ◽  
C. J. Sigurdson ◽  
M. W. Miller ◽  
...  
Keyword(s):  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Odocoileus Hemionus ◽  
Palatine Tonsil ◽  
Spongiform Encephalopathy ◽  
Motor Nucleus ◽  
Serial Sections ◽  
Wasting Disease ◽  
The Brain

Serial sections of brain and palatine tonsil were examined by immunohistochemical staining (IHC) using monoclonal antibody F89/160.1.5 for detecting protease-resistant prion protein (PrPres) in 35 hunterkilled mule deer ( Odocoileus hemionus) with chronic wasting disease. Serial sections of brain were stained with hematoxylin and eosin and examined for spongiform encephalopathy (SE). Clinical signs of disease were not observed in any of these deer. On the basis of the location and abundance of IHC and the location and severity of SE, deer were placed into four categories. Category 1 ( n = 8) was characterized by IHC in the palatine tonsil with no evidence of IHC or SE in the brain. Category 2 ( n = 13) was characterized by IHC in the palatine tonsil and IHC with or without SE in the dorsal motor nucleus of the vagus nerve (DMNV). Category 3 ( n = 2) was characterized by IHC in the palatine tonsil, IHC with SE in the myelencephalon, and IHC without SE in the hypothalamus. Category 4 ( n = 12) was characterized by IHC in the palatine tonsil and IHC with SE throughout the brain. Category 1 may represent early lymphoid tissue localization of PrPres. The DMNV appears to be the most consistent single neuroanatomic site of detectable PrPres. Categories 2–4 may represent a progression of spread of PrPres and SE throughout the brain. IHC in tonsil and brain and SE in brain were not detected in 208 control deer.

scholarly journals Humanized Transgenic Mice Are Resistant to Chronic Wasting Disease Prions From Norwegian Reindeer and Moose

2021 ◽  
Author(s):  
Jonathan D F Wadsworth ◽  
Susan Joiner ◽  
Jacqueline M Linehan ◽  
Kezia Jack ◽  
Huda Al-Doujaily ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Brain Tissue ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathy ◽  
Spongiform Encephalopathy ◽  
Zoonotic Potential ◽  
Wasting Disease ◽  
Human Prion Protein ◽  
Prion Transmission ◽  
Wild Reindeer

Abstract Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy or prion disease affecting cervids. In 2016, the first cases of CWD were reported in Europe in Norwegian wild reindeer and moose. The origin and zoonotic potential of these new prion isolates remain unknown. In this study to investigate zoonotic potential we inoculated brain tissue from CWD-infected Norwegian reindeer and moose into transgenic mice overexpressing human prion protein. After prolonged postinoculation survival periods no evidence for prion transmission was seen, suggesting that the zoonotic potential of these isolates is low.

scholarly journals Survey of Cattle in Northeast Colorado for Evidence of Chronic Wasting Disease: Geographical and High-Risk Targeted Sample

2003 ◽  
Vol 15 (3) ◽  
pp. 274-277 ◽  
Author(s):  
Daniel H. Gould ◽  
James L. Voss ◽  
Michael W. Miller ◽  
Annette M. Bachand ◽  
Bruce A. Cummings ◽  
...  
Keyword(s):  
High Risk ◽  
Large Scale ◽  
Chronic Wasting Disease ◽  
Transmissible Spongiform Encephalopathy ◽  
Proteinase K ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Adult Cattle ◽  
Endemic Areas ◽  
Geographically Targeted

A geographically targeted survey of potentially high-risk, adult cattle in chronic wasting disease (CWD)–endemic areas in Colorado was initiated to assess the possibility of the spread of CWD from deer to cattle under natural conditions. Surveyed cattle were sympatric with free-roaming deer in geographically defined areas where CWD occurs and where CWD prevalence has been estimated. To qualify for inclusion in the survey, cattle had to be at least 4 years old and had to have spent a minimum of 4 years in surveyed areas. Brains from culled cattle were examined microscopically and immunohistochemically for tissue alterations indicative of a transmissible spongiform encephalopathy (TSE). Two hundred sixty-two brains were suitable for evaluation and were found to lack changes indicative of a TSE infection. Prion deposition was not demonstrable using a method involving formic acid and proteinase-K treatment before application of monoclonal antibody to bovine prion protein (F99/97.6.1). Some incidental neuropathologic changes unrelated to those of TSEs were detected. Findings from this study suggest that large-scale spread of CWD from deer to cattle under natural range conditions in CWD-endemic areas of northeast Colorado is unlikely.

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