scholarly journals Human Prion Disease and Relative Risk Associated with Chronic Wasting Disease

2006 ◽  
Vol 12 (10) ◽  
pp. 1527-1535 ◽  
Author(s):  
Samantha MaWhinney ◽  
W. John Pape ◽  
Jeri E. Forster ◽  
C. Alan Anderson ◽  
Patrick Bosque ◽  
...  
Keyword(s):  
Relative Risk ◽  
Prion Disease ◽  
Chronic Wasting Disease ◽  
Human Prion Disease ◽  
Wasting Disease

scholarly journals Dehydration of Prions on Environmentally Relevant Surfaces Protects Them from Inactivation by Freezing and Thawing

2018 ◽  
Vol 92 (8) ◽  
Author(s):  
Qi Yuan ◽  
Glenn Telling ◽  
Shannon L. Bartelt-Hunt ◽  
Jason C. Bartz
Keyword(s):  
Prion Disease ◽  
Disease Transmission ◽  
Protein Misfolding ◽  
Chronic Wasting Disease ◽  
Control Strategies ◽  
Horizontal Transmission ◽  
Freezing And Thawing ◽  
Wasting Disease ◽  
Live Animal ◽  
Weathering Processes

ABSTRACTChronic wasting disease (CWD) is an emerging prion disease in North America. Recent identification of CWD in wild cervids from Norway raises the concern of the spread of CWD in Europe. CWD infectivity can enter the environment through live animal excreta and carcasses where it can bind to soil. Well-characterized hamster prion strains and CWD field isolates in unadsorbed or soil-adsorbed forms that were either hydrated or dehydrated were subjected to repeated rounds of freezing and thawing. We found that 500 cycles of repeated freezing and thawing of hydrated samples significantly decreased the abundance of PrPScand reduced protein misfolding cyclic amplification (PMCA) seeding activity that could be rescued by binding to soil. Importantly, dehydration prior to freezing and thawing treatment largely protected PrPScfrom degradation, and the samples maintained PMCA seeding activity. We hypothesize that redistribution of water molecules during the freezing and thawing process alters the stability of PrPScaggregates. Overall, these results have significant implications for the assessment of prion persistence in the environment.IMPORTANCEPrions excreted into the environment by infected animals, such as elk and deer infected with chronic wasting disease, persist for years and thus facilitate horizontal transmission of the disease. Understanding the fate of prions in the environment is essential to control prion disease transmission. The significance of our study is that it provides information on the possibility of prion degradation and inactivation under natural weathering processes. This information is significant for remediation of prion-contaminated environments and development of prion disease control strategies.

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

mSphere ◽  
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.

scholarly journals Use of environmental sites by mule deer: a proxy for relative risk of chronic wasting disease exposure and transmission

Ecosphere ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
María Fernanda Mejía‐Salazar ◽  
Cheryl L. Waldner ◽  
Yeen Ten Hwang ◽  
Trent K. Bollinger
Keyword(s):  
Relative Risk ◽  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Wasting Disease ◽  
Disease Exposure

scholarly journals Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
S. Jo Moore ◽  
M. Heather West Greenlee ◽  
Naveen Kondru ◽  
Sireesha Manne ◽  
Jodi D. Smith ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Chronic Wasting Disease ◽  
Mouse Bioassay ◽  
Lymphoid Tissues ◽  
Species Barrier ◽  
Wasting Disease ◽  
Disease Agent ◽  
Domestic Swine

ABSTRACT Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as hosts for the agent of CWD is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Crossbred piglets were assigned to three groups, intracranially inoculated (n = 20), orally inoculated (n = 19), and noninoculated (n = 9). At approximately the age at which commercial pigs reach market weight, half of the pigs in each group were culled (“market weight” groups). The remaining pigs (“aged” groups) were allowed to incubate for up to 73 months postinoculation (mpi). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by Western blotting (WB), antigen capture enzyme immunoassay (EIA), immunohistochemistry (IHC), and in vitro real-time quaking-induced conversion (RT-QuIC). Brain samples from selected pigs were also bioassayed in mice expressing porcine prion protein. Four intracranially inoculated aged pigs and one orally inoculated aged pig were positive by EIA, IHC, and/or WB. By RT-QuIC, PrPSc was detected in lymphoid and/or brain tissue from one or more pigs in each inoculated group. The bioassay was positive in four out of five pigs assayed. This study demonstrates that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high. However, detection of infectivity in orally inoculated pigs with a mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity. IMPORTANCE We challenged domestic swine with the chronic wasting disease agent by inoculation directly into the brain (intracranially) or by oral gavage (orally). Disease-associated prion protein (PrPSc) was detected in brain and lymphoid tissues from intracranially and orally inoculated pigs as early as 8 months of age (6 months postinoculation). Only one pig developed clinical neurologic signs suggestive of prion disease. The amount of PrPSc in the brains and lymphoid tissues of positive pigs was small, especially in orally inoculated pigs. Regardless, positive results obtained with orally inoculated pigs suggest that it may be possible for swine to serve as a reservoir for prion disease under natural conditions.

scholarly journals Genetic Depletion of Complement Receptors CD21/35 Prevents Terminal Prion Disease in a Mouse Model of Chronic Wasting Disease

2012 ◽  
Vol 189 (9) ◽  
pp. 4520-4527 ◽  
Author(s):  
Brady Michel ◽  
Adam Ferguson ◽  
Theodore Johnson ◽  
Heather Bender ◽  
Crystal Meyerett-Reid ◽  
...  
Keyword(s):  
Mouse Model ◽  
Prion Disease ◽  
Chronic Wasting Disease ◽  
Complement Receptors ◽  
Wasting Disease

scholarly journals Longitudinal Detection of Prion Shedding in Saliva and Urine by Chronic Wasting Disease-Infected Deer by Real-Time Quaking-Induced Conversion

2015 ◽  
Vol 89 (18) ◽  
pp. 9338-9347 ◽  
Author(s):  
Davin M. Henderson ◽  
Nathaniel D. Denkers ◽  
Clare E. Hoover ◽  
Nina Garbino ◽  
Candace K. Mathiason ◽  
...  
Keyword(s):  
Prion Disease ◽  
Chronic Wasting Disease ◽  
Prion Diseases ◽  
Lethal Dose ◽  
Disease Course ◽  
Wasting Disease ◽  
Daily Production ◽  
Canadian Provinces ◽  
Free Ranging

ABSTRACTChronic wasting disease (CWD) is an emergent, rapidly spreading prion disease of cervids. Shedding of infectious prions in saliva and urine is thought to be an important factor in CWD transmission. To help to elucidate this issue, we applied anin vitroamplification assay to determine the onset, duration, and magnitude of prion shedding in longitudinally collected saliva and urine samples from CWD-exposed white-tailed deer. We detected prion shedding as early as 3 months after CWD exposure and sustained shedding throughout the disease course. We estimated that the 50% lethal dose (LD50) for cervidized transgenic mice would be contained in 1 ml of infected deer saliva or 10 ml of urine. Given the average course of infection and daily production of these body fluids, an infected deer would shed thousands of prion infectious doses over the course of CWD infection. The direct and indirect environmental impacts of this magnitude of prion shedding on cervid and noncervid species are surely significant.IMPORTANCEChronic wasting disease (CWD) is an emerging and uniformly fatal prion disease affecting free-ranging deer and elk and is now recognized in 22 U.S. states and 2 Canadian provinces. It is unique among prion diseases in that it is transmitted naturally through wild populations. A major hypothesis to explain CWD's florid spread is that prions are shed in excreta and transmitted via direct or indirect environmental contact. Here we use a rapidin vitroassay to show that infectious doses of CWD prions are in fact shed throughout the multiyear disease course in deer. This finding is an important advance in assessing the risks posed by shed CWD prions to animals as well as humans.

scholarly journals Generation of human chronic wasting disease in transgenic mice

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Zerui Wang ◽  
Kefeng Qin ◽  
Manuel V. Camacho ◽  
Ignazio Cali ◽  
Jue Yuan ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Prion Disease ◽  
Protein Misfolding ◽  
Chronic Wasting Disease ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Species Barrier ◽  
Wasting Disease ◽  
Bona Fide

AbstractChronic wasting disease (CWD) is a cervid prion disease caused by the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC). It has been spreading rapidly in North America and also found in Asia and Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) is the only animal prion disease known to be zoonotic, the transmissibility of CWD to humans remains uncertain. Here we report the generation of the first CWD-derived infectious human PrPSc by elk CWD PrPSc-seeded conversion of PrPC in normal human brain homogenates using in vitro protein misfolding cyclic amplification (PMCA). Western blotting with human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPSc was derived from the human PrPC substrate. Two lines of humanized transgenic mice expressing human PrP with either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPSc patterns and neuropathological changes in the brain. Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSc can cross the species barrier to convert human PrPC into infectious PrPSc that can produce bona fide prion disease when inoculated into humanized transgenic mice.

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