Bovine Spongiform Encephalopathy (<scp>BSE</scp>)

Brown, Paul; Will, Robert; Bradley, R.; Asher, David M.; Detwiler, Linda A.

doi:10.1002/0471743984.vse1235

Cited by 1 publication

(1 citation statement)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since PrP Sc tends to accumulate in the brains of prion-infected animals with neurons serving as the target, it is only natural that PrP Sc accumulations are selectively located in the neurons of both the central nervous system (CNS) and peripheral nervous system (PNS) [10,32,34,62,137]. However, certain combinations of prion strain and host species show PrP Sc accumulations in not only the CNS and PNS but also other tissues such as the tonsils, spleen, lymphnode, retina, proximal nerves, and gut-associ-ated lymphoid tissues [2,12,37,39,47,89]. In the mouse, PrP Sc accumulates in the lymphoreticular systems (such as the spleen) in an infection route-independent manner before PrP Sc accumulation occurs in the brain, even if the mouse is intracerebrally inoculated [45].…”

Section: Prp Sc Distribution In Tissuesmentioning

confidence: 99%

Recent Developments in Prion Disease Research: Diagnostic Tools and In Vitro Cell Culture Models

Sakudo

Nakamura

Ikuta

et al. 2007

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. After prion infection, an abnormal isoform of prion protein (PrP Sc ) converts the cellular isoform of prion protein (PrP C ) into PrP Sc . PrP C -to-PrP Sc conversion leads to PrP Sc accumulation and PrP C deficiency, contributing etiologically to induction of prion diseases. Presently, most of the diagnostic methods for prion diseases are dependent on PrP Sc detection. Highly sensitive/accurate specific detection of PrP Sc in many different samples is a prerequisite for attempts to develop reliable detection methods. Towards this goal, several methods have recently been developed to facilitate sensitive and precise detection of PrP Sc , namely, protein misfolding cyclic amplification, conformation-dependent immunoassay, dissociation-enhanced lanthanide fluorescent immunoassay, capillary gel electrophoresis, fluorescence correlation spectroscopy, flow microbead immunoassay, etc. Additionally, functionally relevant prion-susceptible cell culture models that recognize the complexity of the mechanisms of prion infection have also been pursued, not only in relation to diagnosis, but also in relation to prion biology. Prion protein (PrP) gene-deficient neuronal cell lines that can clearly elucidate PrP C functions would contribute to understanding of the prion infection mechanism. In this review, we describe the trend in recent development of diagnostic methods and cell culture models for prion diseases and their potential applications in prion biology. Evidence of prion infections has been established by the accumulation of an abnormal isoform of prion protein (PrP Sc ) and/or infectivity after multiple passages [54,85,94,131]. In vitro conversion of the cellular isoform of prion protein (PrP C ) to form PrP Sc -like products has been demonstrated by incubating 35 S-labeled PrP C with PrP Sc . This produced a protease-resistant radioactive product with the mobility of protease-treated authentic PrP Sc [55]. This in vitro conversion confirms the species-[90] and strain-specificities [7] observed in vivo. However, because the yield is less stoichiometric than for PrP Sc [55], it has not been possible to determine whether or not an increase in infectivity occurred [55]. Recent progress in the development of diagnostic methods for PrP Sc detection has dramatically facilitated many approaches in prion biology. The protein misfolding cyclic amplification (PMCA) method deserves special mention [96]. Hitherto, it has not been possible to renature completely denatured prion preparations to an infectious state [79,81]; however, the novel PMCA approach enables in vitro amplification of infectious prions [16].The susceptibility of cell lines, such as N2a, in an in vitro cell culture assay to prion infections has been assessed by exposing the cells to serial dilutions of prion-infected mouse brain homogenates, and the dilution rate yielding negative outcome in a blotting assay for PrP Sc has been determined to be the infectivity level. Prion concentrations equivalent to those determined in an animal bioassay [9] have ...

show abstract