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

Bravo-Risi, Francisca; Soto, P.; Eckland, Thomas; Dittmar, Robert; Ramírez, Santiago Cañardo; Catumbela, Celso S. G.; Soto, Claudio; Lockwood, Mitch A.; Nichols, Tracy A.; Morales, Rodrigo

doi:10.1038/s41598-021-97737-y

Cited by 16 publications

(16 citation statements)

References 48 publications

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“…While our results only begin to uncover the implications of scrapes as a source of indirect contact, they do support the notion that managers should encourage hunters to harvest greater numbers of reproductive‐age males to reduce contamination at scrapes and the degree of indirect contact occurring at them. As new methodologies to detect prions in environmental samples emerge (Bravo‐Risi et al, 2021; Tennant et al, 2020), it will be possible to develop strategies for detecting contaminated scrape sites and reducing the spread of CWD via scrapes.…”

Section: Discussionmentioning

confidence: 99%

Social network analysis of white‐tailed deer scraping behavior: Implications for disease transmission

et al. 2023

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Host contact structure affects pathogen transmission in host populations, but many measures of host contact do not distinguish contacts that are relevant to pathogen transmission from those that are not. Scrapes are sites for chemical communication by white‐tailed deer (Odocoileus virginianus) during the breeding season and potential sites of transmission of prions, the causative agent of chronic wasting disease (CWD). Scrape‐related behaviors vary in their probability of transmitting prions to or from the environment, suggesting that behavior be combined with contact structure to better reflect potential heterogeneity in prion transmission at scrapes. We recorded visits and behaviors by deer at scrapes throughout DeSoto National Wildlife Refuge, Nebraska in 2005 and 2006. We recorded 2013 interactions by 169 unique identifiable males and 75 females. Adult males performed the most scrape‐related behaviors and spent the most time at scrapes, especially smelling the overhanging branch (70%), smelling the scrape (59%), licking/grasping the overhanging branch (44%), and scraping (36%). We used social network analysis to test the effect of behavior on indirect contact networks among deer at scrapes. By weighting edges based on the frequency and duration of behaviors, we produced networks representing sources of variation in scrape use and compared these networks to evaluate the effects of behavior on network contact structure. Social networks based on scrape‐related behavior were highly connected and dependent upon the frequency, duration, and type of behavior exhibited at scrapes (e.g., scraping, interacting with a scrape or overhanging branch, rub‐urinating, grazing) as well as the age of the deer. Accounting for contact frequency produced networks with lower variation in contact, but higher ability to facilitate contact among disparate groups. Including behavior when defining edges did not preserve the network properties of simpler measures (i.e., unweighted networks) suggesting that heterogeneity in behaviors that affect transmission probability is important for inferring transmission networks from contact networks. High connectivity through indirect contacts suggests that scrapes may be effective targets for management. Adult male deer had the highest connectivity, suggesting that management strategies focused on reducing their interaction with scrapes through density reduction or behavioral modification could reduce the connectivity of indirect contact networks.

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Section: Discussionmentioning

confidence: 99%

Social network analysis of white‐tailed deer scraping behavior: Implications for disease transmission

et al. 2023

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“…Although published reports on CWD in captive cervids suggest horizontal transmission is most important, 40 vertical transmission may play a role as well and has been documented in white-tailed deer and elk. 8,45,55…”

Section: Discussionmentioning

confidence: 99%

Distribution of the misfolded isoform of the prion protein in peripheral tissues and spinal cord of Rocky Mountain elk (Cervus elaphus nelsoni) with naturally occurring chronic wasting disease

Spraker

Gidlewski²,

Powers

et al. 2023

Vet Pathol

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Chronic wasting disease (CWD) is an infectious transmissible spongiform encephalopathy of cervids associated with the presence of a misfolded prion protein (PrPCWD). Progression of PrPCWD distribution has been described using immunohistochemistry and histologic changes in a single section of brain stem at the level of the obex resulting in scores from 0 (early) to 10 (terminal) in elk with naturally occurring CWD. Here we describe the spread and distribution of PrPCWD in peripheral tissues and spinal cord in 16 wild and 17 farmed Rocky Mountain elk ( Cervus elaphus nelsoni) with naturally occurring CWD and correlate these findings with obex scores. Spinal cord and approximately 110 peripheral tissues were collected, processed, stained with hematoxylin and eosin, and immunolabeled with the anti-prion protein monoclonal antibody F99/97.6.1. The medial retropharyngeal and tracheobronchial lymph nodes were the first tissues to accumulate PrPCWD, followed by other lymphoid tissues, myenteric plexus, spinal cord, and finally tissues outside of the lymphatic and neural systems. However, the only significant histological lesion observed was mild spongiform encephalopathy in the dorsal column of the lower spinal cord in elk with an obex score of ≥9. Initial exposure to CWD prions may be through the respiratory system and spread appears to occur primarily via the autonomic nervous system. Therefore, we suggest using obex scores as a proxy for stage of disease progression and verifying with key peripheral tissues.

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“…Newer methods of detection are currently being developed such as protein misfolding cyclic amplification (PMCA) and Real Time Quaking Induced Conversion assay (RT-QuIC). PMCA is a sensitive method that amplifies PrP Sc in vivo and has been used to generate CWD seeds for inoculation into human PRNP mouse models (43)(44)(45)(46)(47)(48). RT-QuIC is a highly sensitive test that amplifies misfolded PrP seeds using PrP C substrates (usually from Syrian hamster or bank vole) which form amyloid fibrils and are detectible using a microplate reader (44,45).…”

Section: Chronic Wasting Diseasementioning

confidence: 99%

Mouse models of chronic wasting disease: A review

Cook

Hensley-McBain²,

Grindeland³

2023

Front. Virol.

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Animal models are essential tools for investigating and understanding complex prion diseases like chronic wasting disease (CWD), an infectious prion disease of cervids (elk, deer, moose, and reindeer). Over the past several decades, numerous mouse models have been generated to aid in the advancement of CWD knowledge and comprehension. These models have facilitated the investigation of pathogenesis, transmission, and potential therapies for CWD. Findings have impacted CWD management and disease outcomes, though much remains unknown, and a cure has yet to be discovered. Studying wildlife for CWD effects is singularly difficult due to the long incubation time, subtle clinical signs at early stages, lack of convenient in-the-field live testing methods, and lack of reproducibility of a controlled laboratory setting. Mouse models in many cases is the first step to understanding the mechanisms of disease in a shortened time frame. Here, we provide a comprehensive review of studies with mouse models in CWD research. We begin by reviewing studies that examined the use of mouse models for bioassays for tissues, bodily fluids, and excreta that spread disease, then address routes of infectivity and infectious load. Next, we delve into studies of genetic factors that influence protein structure. We then move on to immune factors, possible transmission through environmental contamination, and species barriers and differing prion strains. We conclude with studies that make use of cervidized mouse models in the search for therapies for CWD.

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

Cited by 16 publications

References 48 publications

Social network analysis of white‐tailed deer scraping behavior: Implications for disease transmission

Social network analysis of white‐tailed deer scraping behavior: Implications for disease transmission

Distribution of the misfolded isoform of the prion protein in peripheral tissues and spinal cord of Rocky Mountain elk (Cervus elaphus nelsoni) with naturally occurring chronic wasting disease

Mouse models of chronic wasting disease: A review

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