scholarly journals Unique Structural Features of Mule Deer Prion Protein Provide Insights into Chronic Wasting Disease

ACS Omega ◽  
2019 ◽  
Vol 4 (22) ◽  
pp. 19913-19924 ◽  
Author(s):  
Urška Slapšak ◽  
Giulia Salzano ◽  
Gregor Ilc ◽  
Gabriele Giachin ◽  
Jifeng Bian ◽  
...  
Keyword(s):  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Structural Features ◽  
Wasting Disease

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.

scholarly journals Prion protein in cardiac muscle of elk (Cervus elaphus nelsoni) and white-tailed deer (Odocoileus virginianus) infected with chronic wasting disease

2006 ◽  
Vol 87 (11) ◽  
pp. 3443-3450 ◽  
Author(s):  
Jean E. Jewell ◽  
Jeremy Brown ◽  
Terry Kreeger ◽  
Elizabeth S. Williams
Keyword(s):  
Western Blot ◽  
Odocoileus Virginianus ◽  
Prion Protein ◽  
Cervus Elaphus ◽  
Chronic Wasting Disease ◽  
Striated Muscle ◽  
Mule Deer ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Cervus Elaphus Nelsoni

To investigate the possible presence of disease-associated prion protein (PrPd) in striated muscle of chronic wasting disease (CWD)-affected cervids, samples of diaphragm, tongue, heart and three appendicular skeletal muscles from mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus), elk (Cervus elaphus nelsoni) and moose (Alces alces shirasi) were examined by ELISA, Western immunoblot and immunohistochemistry (IHC). PrPd was detected in samples of heart muscle from seven of 16 CWD-infected white-tailed deer, including one free-ranging deer, and in 12 of 17 CWD-infected elk, but not in any of 13 mule deer samples, nor in the single CWD-infected moose. For white-tailed deer, PrPd was detected by Western blot at multiple sites throughout the heart; IHC results on ventricular sections of both elk and white-tailed deer showed positive staining in cardiac myocytes, but not in conduction tissues or nerve ganglia. Levels of PrPd in cardiac tissues were estimated from Western blot band intensity to be lower than levels found in brain tissue. PrPd was not detected in diaphragm, triceps brachii, semitendinosus, latissiumus dorsi or tongue muscles for any of the study subjects. This is the first report of PrPd in cardiac tissue from transmissible spongiform encephalopathy-infected ruminants in the human food chain and the first demonstration by immunological assays of PrPd in any striated muscle of CWD-infected cervids.

Deposition patterns of disease-associated prion protein in captive mule deer brains with chronic wasting disease

2001 ◽  
Vol 102 (5) ◽  
pp. 496-500 ◽  
Author(s):  
Pawel P. Liberski ◽  
Don C. Guiroy ◽  
Elizabeth S. Williams ◽  
Anna Walis ◽  
Herbert Budka
Keyword(s):  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Wasting Disease ◽  
Deposition Patterns

scholarly journals Transmission of Prions from Mule Deer and Elk with Chronic Wasting Disease to Transgenic Mice Expressing Cervid PrP

2004 ◽  
Vol 78 (23) ◽  
pp. 13345-13350 ◽  
Author(s):  
Shawn R. Browning ◽  
Gary L. Mason ◽  
Tanya Seward ◽  
Mike Green ◽  
Gwyneth A. J. Eliason ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Prion Protein ◽  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Amyloid Plaques ◽  
Neurological Dysfunction ◽  
Wasting Disease ◽  
Prion Strain ◽  
Spongiform Degeneration ◽  
Transmission Studies

ABSTRACT We generated mice expressing cervid prion protein to produce a transgenic system simulating chronic wasting disease (CWD) in deer and elk. While normal mice were resistant to CWD, these transgenic mice uniformly developed signs of neurological dysfunction ∼230 days following intracerebral inoculation with four CWD isolates. Inoculated transgenic mice homozygous for the transgene array developed disease after ∼160 days. The brains of sick transgenic mice exhibited widespread spongiform degeneration and contained abnormal prion protein and abundant amyloid plaques, many of which were florid plaques. Transmission studies indicated that the same prion strain caused CWD in the analyzed mule deer and elk. These mice provide a new and reliable tool for detecting CWD prions.

scholarly journals Chronic Wasting Disease: Evolution of Diagnostic Testing for a Naturally Occurring Prion Disease

2017 ◽  
Author(s):  
Nicholas J. Haley ◽  
Juergen A. Richt
Keyword(s):  
Prion Protein ◽  
Protein Misfolding ◽  
Chronic Wasting Disease ◽  
Mule Deer ◽  
The United States ◽  
Alpha Synuclein ◽  
Wasting Disease ◽  
Disease Evolution ◽  
Naturally Occurring

Since chronic wasting disease (CWD) was first identified nearly 50 years ago in a captive mule deer herd in the Rocky Mountains of the United States, it has slowly spread across North America through the natural and anthropogenic movement of cervids and their carcasses.  As the endemic areas have expanded, so has the need for rapid, sensitive, and cost effective diagnostic tests – especially those which take advantage of samples collected antemortem.  Over the past two decades, strategies have evolved from the recognition of microscopic spongiform pathology and associated immunohistochemical staining of the misfolded prion protein to enzyme-linked immunoassays capable of detecting the abnormal prion conformer in postmortem samples.  In a history that parallels the diagnosis of more conventional infectious agents, both qualitative and real-time amplification assays have recently been developed to detect minute quantities of misfolded prions in a range of biological and environmental samples.  With these more sensitive and semi-quantitative approaches has come a greater understanding of the pathogenesis and epidemiology of this disease in the native host.  Because the molecular pathogenesis of prion protein misfolding is broadly analogous to the misfolding of other pathogenic proteins, including Aβ and α-synuclein, efforts are currently underway to apply these in vitro amplification techniques towards the diagnosis of Alzheimer’s disease, Parkinson’s disease, and other proteinopathies.   Chronic wasting disease – once a rare disease of Colorado mule deer – now represents one of the few naturally occurring protein misfolding disorders which might allow continued development and implementation of novel diagnostic strategies in an animal model.

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 Efficient In Vitro Amplification of Chronic Wasting Disease PrPRES

2007 ◽  
Vol 81 (17) ◽  
pp. 9605-9608 ◽  
Author(s):  
Timothy D. Kurt ◽  
Matthew R. Perrott ◽  
Carol J. Wilusz ◽  
Jeffrey Wilusz ◽  
Surachai Supattapone ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Prion Protein ◽  
Protein Misfolding ◽  
Chronic Wasting Disease ◽  
Body Fluids ◽  
The Body ◽  
Wasting Disease ◽  
Highly Efficient ◽  
Significant Step

ABSTRACT Chronic wasting disease (CWD) of cervids is associated with conversion of the normal cervid prion protein, PrPC, to a protease-resistant conformer, PrPCWD. Here we report the use of both nondenaturing amplification and protein-misfolding cyclic amplification (PMCA) to amplify PrPCWD in vitro. Normal brains from deer, transgenic mice expressing cervid PrPC [Tg(cerPrP)1536 mice], and ferrets supported amplification. PMCA using normal Tg(cerPrP)1536 brains as the PrPC substrate produced >6.5 × 109-fold amplification after six rounds. Highly efficient in vitro amplification of PrPCWD is a significant step toward detection of PrPCWD in the body fluids or excreta of CWD-susceptible species.

scholarly journals Tonsillar Biopsy Test for Chronic Wasting Disease: Two Sampling Approaches in Mule Deer and White-tailed Deer

2005 ◽  
Vol 41 (4) ◽  
pp. 820-824 ◽  
Author(s):  
Krysten L. Schuler ◽  
Jonathan A. Jenks ◽  
Christopher S. DePerno ◽  
Margaret A. Wild ◽  
Christopher C. Swanson
Keyword(s):  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Wasting Disease
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