Correlation between Infectivity and Disease Associated Prion Protein in the Nervous System and Selected Edible Tissues of Naturally Affected Scrapie Sheep

被引：12

作者：

Chianini, Francesca ^{[1
]}

Cosseddu, Gian Mario ^{[2
]}

Steele, Philip ^{[1
]}

Hamilton, Scott ^{[1
]}

Hawthorn, Jeremy ^{[3
]}

Siso, Silvia ^{[4
]}

Pang, Yvonne ^{[1
]}

Finlayson, Jeanie ^{[1
]}

Eaton, Samantha L. ^{[1
]}

Reid, Hugh W. ^{[1
]}

Dagleish, Mark P. ^{[1
]}

Di Bari, Michele Angelo ^{[2
]}

D'Agostino, Claudia ^{[2
]}

Agrimi, Umberto ^{[2
]}

Terry, Linda ^{[3
]}

Nonno, Romolo ^{[2
]}

机构：

[1] Moredun Res Inst, Penicuik EH26 0PZ, Midlothian, Scotland

[2] Ist Super Sanita, Dept Food Safety & Vet Publ Hlth, I-00161 Rome, Italy

[3] Anim & Plant Hlth Agcy APHA Weybridge, Addlestone KT15 3NB, Surrey, England

[4] Anim & Plant Hlth Agcy APHA Lasswade, Penicuik EH26 0PZ, Midlothian, Scotland

来源：

PLOS ONE | 2015年 / 10卷 / 03期

关键词：

BOVINE SPONGIFORM ENCEPHALOPATHY; CHRONIC WASTING DISEASE; SUFFOLK SHEEP; PRECLINICAL SCRAPIE; PRP ACCUMULATION; DIAGNOSIS; PATHOGENESIS; KIDNEYS; GLAREOLUS; GENOTYPE;

D O I：

10.1371/journal.pone.0122785

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative disorders characterised by the accumulation of a pathological form of a host protein known as prion protein (PrP). The validation of abnormal PrP detection techniques is fundamental to allow the use of high-throughput laboratory based tests, avoiding the limitations of bioassays. We used scrapie, a prototype TSE, to examine the relationship between infectivity and laboratory based diagnostic tools. The data may help to optimise strategies to prevent exposure of humans to small ruminant TSE material via the food chain. Abnormal PrP distribution/accumulation was assessed by immunohistochemistry (IHC), Western blot (WB) and ELISA in samples from four animals. In addition, infectivity was detected using a sensitive bank vole bioassay with selected samples from two of the four sheep and protein misfolding cyclic amplification using bank vole brain as substrate (vPMCA) was also carried out in selected samples from one animal. Lymph nodes, oculomotor muscles, sciatic nerve and kidney were positive by IHC, WB and ELISA, although at levels 100-1000 fold lower than the brain, and contained detectable infectivity by bioassay. Tissues not infectious by bioassay were also negative by all laboratory tests including PMCA. Although discrepancies were observed in tissues with very low levels of abnormal PrP, there was an overall good correlation between IHC, WB, ELISA and bioassay results. Most importantly, there was a good correlation between the detection of abnormal PrP in tissues using laboratory tests and the levels of infectivity even when the titre was low. These findings provide useful information for risk modellers and represent a first step toward the validation of laboratory tests used to quantify prion infectivity, which would greatly aid TSE risk assessment policies.

引用

页数：21