scholarly journals Detection of CWD prions in naturally infected white-tailed deer fetuses and gestational tissues by PMCA

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Francisca Bravo-Risi ◽  
Paulina Soto ◽  
Thomas Eckland ◽  
Robert Dittmar ◽  
Santiago Ramírez ◽  
...  
Keyword(s):  
Vertical Transmission ◽  
Prion Disease ◽  
Protein Misfolding ◽  
Animal Species ◽  
Wasting Disease ◽  
Future Studies ◽  
Fetal Tissues ◽  
Indirect Exposure ◽  
Animal Contact ◽  
Gestational Tissues

AbstractChronic wasting disease (CWD) is a prevalent prion disease affecting cervids. CWD is thought to be transmitted through direct animal contact or by indirect exposure to contaminated environmental fomites. Other mechanisms of propagation such as vertical and maternal transmissions have also been suggested using naturally and experimentally infected animals. Here, we describe the detection of CWD prions in naturally-infected, farmed white-tailed deer (WTD) fetal tissues using the Protein Misfolding Cyclic Amplification (PMCA) technique. Prion seeding activity was identified in a variety of gestational and fetal tissues. Future studies should demonstrate if prions present in fetuses are at sufficient quantities to cause CWD after birth. This data confirms previous findings in other animal species and furthers vertical transmission as a relevant mechanism of CWD dissemination.

scholarly journals Detection of Chronic Wasting Disease Prions in Fetal Tissues of Free-Ranging White-Tailed Deer

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2430
Author(s):  
Amy V. Nalls ◽  
Erin E. McNulty ◽  
Amber Mayfield ◽  
James M. Crum ◽  
M. Kevin Keel ◽  
...  
Keyword(s):  
North America ◽  
Vertical Transmission ◽  
Protein Misfolding ◽  
Chronic Wasting Disease ◽  
Wasting Disease ◽  
Indirect Contact ◽  
Fetal Tissues ◽  
Animal Exposure ◽  
Asymptomatic Phase ◽  
Free Ranging

The transmission of chronic wasting disease (CWD) has largely been attributed to contact with infectious prions shed in excretions (saliva, urine, feces, blood) by direct animal-to-animal exposure or indirect contact with the environment. Less-well studied has been the role that mother-to-offspring transmission may play in the facile transmission of CWD, and whether mother-to-offspring transmission before birth may contribute to the extensive spread of CWD. We thereby focused on a population of free-ranging white-tailed deer from West Virginia, USA, in which CWD has been detected. Fetal tissues, ranging from 113 to 158 days of gestation, were harvested from the uteri of CWD+ dams in the asymptomatic phase of infection. Using serial protein misfolding amplification (sPMCA), we detected evidence of prion seeds in 7 of 14 fetuses (50%) from 7 of 9 pregnancies (78%), with the earliest detection at 113 gestational days. This is the first report of CWD detection in free ranging white-tailed deer fetal tissues. Further investigation within cervid populations across North America will help define the role and impact of mother-to-offspring vertical transmission of CWD.

scholarly journals Detection of Chronic Wasting Disease prions in fetal tissues of free-ranging white-tailed deer

2021 ◽  
Author(s):  
AV Nalls ◽  
EE McNulty ◽  
A Mayfield ◽  
JM Crum ◽  
MK Keel ◽  
...  
Keyword(s):  
North America ◽  
Vertical Transmission ◽  
Protein Misfolding ◽  
Chronic Wasting Disease ◽  
Wasting Disease ◽  
Indirect Contact ◽  
Fetal Tissues ◽  
Animal Exposure ◽  
Asymptomatic Phase ◽  
Free Ranging

AbstractThe transmission of chronic wasting disease (CWD) has largely been attributed to contact with infectious prions shed in excretions (saliva, urine, feces, blood) by direct animal-to-animal exposure or indirect contact with the environment. Less-well studied has been the role mother-to-offspring transmission may play in the facile transmission of CWD. We asked whether such extensive spread may also be due to mother-to-offspring transmission, perhaps before birth. We thereby focused on a population of white-tailed deer from West Virginia, USA, in which CWD has been detected. Fetal tissues, ranging from 113 to 158 days of gestation, were harvested from the uteri of CWD+ dams in the asymptomatic phase of infection. Using serial protein misfolding amplification (sPMCA), we detected evidence of prion seeds in 6 of 14 in utero harvested fetuses, with earliest detection at 113 gestational days. This is the first report of CWD detection in free ranging white-tailed deer fetal tissues. Further investigation within cervid populations across North America will help define the role and impact of mother-to-offspring vertical transmission of CWD.

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 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.

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 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 A Short Report on the Extent of Stone Handling Behavior Across Otter Species

2021 ◽  
Vol 8 (1) ◽  
pp. 15-22
Author(s):  
Elisa Bandini
Keyword(s):  
Tool Use ◽  
Animal Species ◽  
Potential Functions ◽  
Play Behavior ◽  
Stone Tool ◽  
Short Report ◽  
Selection Pressures ◽  
Future Studies ◽  
Macaque Species

Animal stone-handling behavior (SH) has been recorded in detail only in primates, mainly across macaque species. The purpose(s) of SH are still unknown, yet various hypotheses have been suggested, including that it is a misdirected behavior when hungry and/or a play behavior that aids individuals' motor and stone tool-use development. SH has also been observed across both wild and captive otter species, but no overview report of the extent of this behavior across otter species has been published yet. To fill this gap in the literature, we contacted wild and captive otter researchers and keepers to enquire directly on SH in the species they work with. We accepted anecdotal reports in this first review of the behavior. Using the reports and anecdotes thus obtained, we compiled the first list of otter species that show SH. We found that most (10 out of 13) of currently known otter species practice SH. Therefore, similarly to macaques, SH is also common in otters and occurs in the majority of species. Future studies should focus on replicating these findings and further investigating the potential functions and selection pressures of SH in otters and other animal species.

scholarly journals Efficient interspecies transmission of synthetic prions

2021 ◽  
Vol 17 (7) ◽  
pp. e1009765
Author(s):  
Alyssa J. Block ◽  
Ronald A. Shikiya ◽  
Thomas E. Eckland ◽  
Anthony E. Kincaid ◽  
Ryan W. Walters ◽  
...  
Keyword(s):  
Prion Disease ◽  
Protein Misfolding ◽  
Conformational Stability ◽  
Cellular Protein ◽  
Interspecies Transmission ◽  
Species Barrier ◽  
Single Strain ◽  
Clinical Onset ◽  
Bona Fide

Prions are comprised solely of PrPSc, the misfolded self-propagating conformation of the cellular protein, PrPC. Synthetic prions are generated in vitro from minimal components and cause bona fide prion disease in animals. It is unknown, however, if synthetic prions can cross the species barrier following interspecies transmission. To investigate this, we inoculated Syrian hamsters with murine synthetic prions. We found that all the animals inoculated with murine synthetic prions developed prion disease characterized by a striking uniformity of clinical onset and signs of disease. Serial intraspecies transmission resulted in a rapid adaptation to hamsters. During the adaptation process, PrPSc electrophoretic migration, glycoform ratios, conformational stability and biological activity as measured by protein misfolding cyclic amplification remained constant. Interestingly, the strain that emerged shares a strikingly similar transmission history, incubation period, clinical course of disease, pathology and biochemical and biological features of PrPSc with 139H, a hamster adapted form of the murine strain 139A. Combined, these data suggest that murine synthetic prions are comprised of bona fide PrPSc with 139A-like strain properties that efficiently crosses the species barrier and rapidly adapts to hamsters resulting in the emergence of a single strain. The efficiency and specificity of interspecies transmission of murine synthetic prions to hamsters, with relevance to brain derived prions, could be a useful model for identification of structure function relationships between PrPSc and PrPC from different species.

scholarly journals Prion protein and prion disease at a glance

2021 ◽  
Vol 134 (17) ◽  
Author(s):  
Caihong Zhu ◽  
Adriano Aguzzi
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Neurodegenerative Disorders ◽  
Prion Diseases ◽  
Amyloid Β ◽  
Cellular Prion Protein ◽  
Future Studies ◽  
Associated Proteins ◽  
Main Component ◽  
Conformational Conversion

ABSTRACT Prion diseases are neurodegenerative disorders caused by conformational conversion of the cellular prion protein (PrPC) into scrapie prion protein (PrPSc). As the main component of prion, PrPSc acts as an infectious template that recruits and converts normal cellular PrPC into its pathogenic, misfolded isoform. Intriguingly, the phenomenon of prionoid, or prion-like, spread has also been observed in many other disease-associated proteins, such as amyloid β (Aβ), tau and α-synuclein. This Cell Science at a Glance and the accompanying poster highlight recently described physiological roles of prion protein and the advanced understanding of pathogenesis of prion disease they have afforded. Importantly, prion protein may also be involved in the pathogenesis of other neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Therapeutic studies of prion disease have also exploited novel strategies to combat these devastating diseases. Future studies on prion protein and prion disease will deepen our understanding of the pathogenesis of a broad spectrum of neurodegenerative conditions.

The neuroepidemiology of human prion disease

2020 ◽  
pp. 367-378
Author(s):  
Patrick JM Urwin ◽  
Anna M Molesworth
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Prion Protein Gene ◽  
Human Prion Disease ◽  
Disease States ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Sporadic Disease

Human prion diseases comprise a number of rare and fatal neurodegenerative conditions that result from the accumulation in the central nervous system of an abnormal form of a naturally occurring protein, called the prion protein. The diseases occur in genetic, sporadic, and acquired forms: genetic disease is associated with mutations in the prion protein gene (PRNP); sporadic disease is thought to result from a spontaneous protein misfolding event; acquired disease results from transmission of infection from an animal or another human. The potential transmissibility of the prion in any of these forms, either in disease states or during the incubation period, has implications for public health. Here we focus on Creutzfeldt-Jakob Disease (CJD), including variant Creutzfeldt-Jakob Disease (vCJD), although we will also discuss other forms of human prion disease.

Sign in / Sign up

Export Citation Format

Share Document