Bone marrow infectivity in cattle exposed to the bovine spongiform encephalopathy agent

Sohn, Hyun‐Joo; Lee, Y. H.; Green, R. B.; Spencer, Y. I.; Hawkins, S. A. C.; Stack, M.J.; Konold, Timm; Wells, G. A. H.; Matthews, D.; Cho, I. S.; Joo, Yi-Seok

doi:10.1136/vr.164.9.272

Cited by 18 publications

(20 citation statements)

References 13 publications

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“…Of the postmortem tests used for BSE diagnosis [13,21], IHC for PrP d with antibody R145 on sections of the medulla at the obex was, as previously indicated, the most sensitive confirmatory method [23]. Previously examined additional immunolabelled sections of brainstem (study 1) [23], or the additional immunolabelled sections of brainstem and rostral brain regions from all cattle in study 2, did not alter the diagnosis based solely on examination of medulla at the obex.…”

Section: Resultsmentioning

confidence: 99%

“…The tests used for BSE diagnosis have been described elsewhere [13,21] and included those used for the statutory confirmation of BSE in the UK surveillance programme. Sections of the medulla at the obex were stained with haematoxylin and eosin for HP and immunolabelled with antibody R145 for detection of PrP d by IHC.…”

Section: Methodsmentioning

confidence: 99%

“…In addition to further brainstem sections, cerebellum, thalamus, corpus striatum and cerebral cortex were similarly examined from all cattle in study 2 as described previously for selected cases [21]. …”

Section: Methodsmentioning

confidence: 99%

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Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent

Konold

Sayers²,

Sach

et al. 2010

BMC Vet Res

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BackgroundVarious clinical protocols have been developed to aid in the clinical diagnosis of classical bovine spongiform encephalopathy (BSE), which is confirmed by postmortem examinations based on vacuolation and accumulation of disease-associated prion protein (PrPd) in the brain. The present study investigated the occurrence and progression of sixty selected clinical signs and behaviour combinations in 513 experimentally exposed cattle subsequently categorised postmortem as confirmed or unconfirmed BSE cases. Appropriate undosed or saline inoculated controls were examined similarly and the data analysed to explore the possible occurrence of BSE-specific clinical expression in animals unconfirmed by postmortem examinations.ResultsBased on the display of selected behavioural, sensory and locomotor changes, 20 (67%) orally dosed and 17 (77%) intracerebrally inoculated pathologically confirmed BSE cases and 21 (13%) orally dosed and 18 (6%) intracerebrally inoculated but unconfirmed cases were considered clinical BSE suspects. None of 103 controls showed significant signs and were all negative on diagnostic postmortem examinations. Signs indicative of BSE suspects, particularly over-reactivity and ataxia, were more frequently displayed in confirmed cases with vacuolar changes in the brain. The display of several BSE-associated signs over time, including repeated startle responses and nervousness, was significantly more frequent in confirmed BSE cases compared to controls, but these two signs were also significantly more frequent in orally dosed cattle unconfirmed by postmortem examinations.ConclusionsThe findings confirm that in experimentally infected cattle clinical abnormalities indicative of BSE are accompanied by vacuolar changes and PrPd accumulation in the brainstem. The presence of more frequently expressed signs in cases with vacuolar changes is consistent with this pathology representing a more advanced stage of disease. That BSE-like signs or sign combinations occur in inoculated animals that were not confirmed as BSE cases by postmortem examinations requires further study to investigate the potential causal relationship with prion disease.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent

Konold

Sayers²,

Sach

et al. 2010

BMC Vet Res

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“…12 A recent experiment on bone marrow infectivity of cattle orally inoculated with BSE used IC inoculation of cattle as a bioassay with sternal bone marrow collected at 22, 26, 32, and 36 months after exposure and found no evidence of BSE in cattle 70-91 months post inoculation, suggesting that disease-causing BSE material in bone marrow is either a rare event or that it may be consistently present but at levels undetectable by what is perhaps considered the most sensitive bioassay (i.e., IC inoculation of cattle). 97 The consistent detectable tissue distribution of PrP d in cattle experimentally inoculated with BSE, TME, CWD, or scrapie is essentially restricted to the bovine nervous system, [24][25][26]37,38,40,42,94 as has been reported in naturally occurring cases of BSE. 17 Bovine tissue infectivity studies in transgenic mice that are highly sensitive to BSE have confirmed the essential restriction of infectivity to the nervous system in clinically diseased BSE cattle.…”

Section: Host Species Exerts Influence Over Prp D Tissue Distributionmentioning

confidence: 94%

Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle

et al. 2011

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Abstract. Prion diseases or transmissible spongiform encephalopathies (TSEs) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of deer, elk and moose; and bovine spongiform encephalopathy (BSE) of cattle. The emergence of BSE and its spread to human beings in the form of variant Creutzfeldt-Jakob disease (vCJD) resulted in interest in susceptibility of cattle to CWD, TME and scrapie. Experimental cross-species transmission of TSE agents provides valuable information for potential host ranges of known TSEs. Some interspecies transmission studies have been conducted by inoculating disease-causing prions intracerebrally (IC) rather than orally; the latter is generally effective in intraspecies transmission studies and is considered a natural route by which animals acquire TSEs. The "species barrier" concept for TSEs resulted from unsuccessful interspecies oral transmission attempts. Oral inoculation of prions mimics the natural disease pathogenesis route whereas IC inoculation is rather artificial; however, it is very efficient since it requires smaller dosage of inoculum, and typically results in higher attack rates and reduces incubation time compared to oral transmission. A species resistant to a TSE by IC inoculation would have negligible potential for successful oral transmission. To date, results indicate that cattle are susceptible to IC inoculation of scrapie, TME, and CWD but it is only when inoculated with TME do they develop spongiform lesions or clinical disease similar to BSE. Importantly, cattle are resistant to oral transmission of scrapie or CWD; susceptibility of cattle to oral transmission of TME is not yet determined.

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“…74(10): 1377-1380, 2012 Chronic wasting disease (CWD) is a neurodegenerative disorder in cervids and a member of the transmissible spongiform encephalopathies (TSEs), also known as prion diseases. TSEs are characterized by abnormal prion proteins (PrP Sc ) acting as infectious agents, which are generated by posttranslational modification of normal prion proteins (PrP C ) that accumulate in the brain and lead to diseases [10,13]. No TSEs have been found in any animal species in the Republic of Korea except for CWD, which is known to have originated from imported elk from Canada [12].…”

mentioning

confidence: 99%

Establishment of a Cell Line Persistently Infected with Chronic Wasting Disease Prions

Kim

Tark

Lee

et al. 2012

The Journal of Veterinary Medical Science

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ABSTRACT. Elk prion protein (PrP C ) has been confirmed to be capable of rendering rabbit epithelial RK13 cells permissive to temporal infection by chronic wasting disease (CWD) prions. The present study satisfactorily generated persistently CWD prion-affected RK13 cells (RKC1-11) using elk PrP C expressing cells (elkRK13) that were generated via the lentiviral expression system with high efficiency. The elkRK13 cells have been shown to be permissive to accumulation of abnormal isoforms of prion protein (PrP Sc ) resulting from CWD prions up to 97 serial passages thus far. This novel prion-affected cell line will help facilitate investigation of the molecular basis of CWD prion pathogenesis and confirmation of CWD prion infectivity in vitro. KEY WORDS: CWD, infection, lentivirus, prion, RK13 cells. doi: 10.1292/jvms.12-0061; J. Vet. Med. Sci. 74(10): 1377-1380, 2012 Chronic wasting disease (CWD) is a neurodegenerative disorder in cervids and a member of the transmissible spongiform encephalopathies (TSEs), also known as prion diseases. TSEs are characterized by abnormal prion proteins (PrP Sc ) acting as infectious agents, which are generated by posttranslational modification of normal prion proteins (PrP C ) that accumulate in the brain and lead to diseases [10,13]. No TSEs have been found in any animal species in the Republic of Korea except for CWD, which is known to have originated from imported elk from Canada [12]. National CWD surveillance has been conducted since 2001, and subsequent cases were found in farmed elk in 2004 and 2005 [6]. More recently, CWD cases were detected in farmed elk, sika deer, red deer, and crossbred sika and red deer in 2010. This is the first report of natural CWD cases in red deer and sika deer (unpublished data). Epidemiologically speaking, it is possible that these indigenous CWD cases are associated with the imported CWD-affected elk.Several lines of persistently prion-affected cells have represented relevant and useful experimental models [14]. Mouse neuroblastoma cell lines (N2a) are the most commonly used; however, their use is limited by the fact that they are susceptible only to mouse-adapted prion strains. In contrast, rabbit kidney epithelial cells (RK13), which overexpress exogenous sheep PrP C , have been confirmed to be susceptible to natural sheep scrapie [3]. On the other hand, CWD prion persistently infected cell lines have been established from transformed primary mule deer brain cells [11]. Attempts to establish persistent CWD prion infection in a cell line have previously been unsuccessful, resulting in transient PrP Sc accumulation in elk PrP C -expressing RK13 cells [1].In this study, we attempted to establish a CWD prion persistently infected cell line to help characterize CWD prions, which are currently causing sporadic disease in South Korea. We tested the lentiviral protein expression system [5] as an approach method because it has broad tropism to a range of species and cell types, a stably expressed cell line is easily selected using safe laboratory ...

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Bone marrow infectivity in cattle exposed to the bovine spongiform encephalopathy agent

Cited by 18 publications

References 13 publications

Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent

Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent

Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle

Establishment of a Cell Line Persistently Infected with Chronic Wasting Disease Prions

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