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

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.

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

Journal of General Virology ◽

10.1099/0022-1317-80-10-2757 ◽

1999 ◽

Vol 80 (10) ◽

pp. 2757-2764 ◽

Cited By ~ 210

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.

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

Veterinary Pathology ◽

10.1177/030098589303000105 ◽

1993 ◽

Vol 30 (1) ◽

pp. 36-45 ◽

Cited By ~ 93

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.

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

Veterinary Pathology ◽

10.1354/vp.39-5-546 ◽

2002 ◽

Vol 39 (5) ◽

pp. 546-556 ◽

Cited By ~ 51

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.

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Comparison of Histological Lesions and Immunohistochemical Staining of Proteinase-resistant Prion Protein in a Naturally Occurring Spongiform Encephalopathy of Free-ranging Mule Deer (Odocoileus hemionus) with Those of Chronic Wasting Disease of Captive Mule Deer

Veterinary Pathology ◽

10.1354/vp.39-1-110 ◽

2002 ◽

Vol 39 (1) ◽

pp. 110-119 ◽

Cited By ~ 66

Author(s):

T. R. Spraker ◽

R. R. Zink ◽

B. A. Cummings ◽

M. A. Wild ◽

M. W. Miller ◽

...

Keyword(s):

Prion Protein ◽

Immunohistochemical Staining ◽

Chronic Wasting Disease ◽

Mule Deer ◽

Odocoileus Hemionus ◽

Spongiform Encephalopathy ◽

Wasting Disease ◽

Naturally Occurring ◽

Free Ranging

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

Journal of General Virology ◽

10.1099/0022-1317-83-10-2629 ◽

2002 ◽

Vol 83 (10) ◽

pp. 2629-2634 ◽

Cited By ~ 48

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.

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Failure To Detect Prion Infectivity in Ticks following Prion-Infected Blood Meal

mSphere ◽

10.1128/msphere.00741-20 ◽

2020 ◽

Vol 5 (5) ◽

Author(s):

Ronald A. Shikiya ◽

Anthony E. Kincaid ◽

Jason C. Bartz ◽

Travis J. Bourret

Keyword(s):

Prion Disease ◽

Blood Meal ◽

Red Deer ◽

Chronic Wasting Disease ◽

Mule Deer ◽

Geographic Range ◽

Lymphoid Tissues ◽

Wasting Disease ◽

Prion Infection ◽

Prion Infectivity

ABSTRACT Chronic wasting disease (CWD) is an emerging and fatal contagious prion disease that affects cervids, including mule deer, white-tailed deer, black-tailed deer, red deer reindeer, elk, and moose. CWD prions are widely distributed throughout the bodies of CWD-infected animals and are found in the nervous system, lymphoid tissues, muscle, blood, urine, feces, and antler velvet. The mechanism of CWD transmission in natural settings is unknown. Potential mechanisms of transmission include horizontal, maternal, or environmental routes. Due to the presence of prions in the blood of CWD-infected animals, the potential exists for invertebrates that feed on mammalian blood to contribute to the transmission of CWD. The geographic range of the Rocky Mountain Wood tick, Dermancentor andersoni, overlaps with CWD throughout the northwest United States and southwest Canada, raising the possibility that D. andersoni parasitization of cervids may be involved in CWD transmission. We investigated this possibility by examining the blood meal of D. andersoni that fed upon prion-infected hamsters for the presence of prion infectivity by animal bioassay. None of the hamsters inoculated with a D. andersoni blood meal that had been ingested from prion-infected hamsters developed clinical signs of prion disease or had evidence for a subclinical prion infection. Overall, the data do not demonstrate a role for D. andersoni in the transmission of prion disease. IMPORTANCE Chronic wasting disease (CWD) is an emerging prion disease that affects cervids, including mule deer, white-tailed deer, black-tailed deer, red deer reindeer, elk, and moose. The mechanism of CWD transmission in unknown. Due to the presence of prions in the blood of CWD-infected animals, it is possible for invertebrates that feed on cervid blood to contribute to the transmission of CWD. We examined the blood meal of D. andersoni, a tick with a similar geographic range as cervids, that fed upon prion-infected hamsters for the presence of prion infectivity by animal bioassay. None of the D. andersoni blood meals that had been ingested from prion-infected hamsters yielded evidence of prion infection. Overall, the data do not support a role of D. andersoni in the transmission of prion disease.

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

Journal of Virology ◽

10.1128/jvi.80.2.596-604.2006 ◽

2006 ◽

Vol 80 (2) ◽

pp. 596-604 ◽

Cited By ~ 48

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.

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