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Volume 20, Number 1—January 2014

Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease

Jean Yves Douet, Saima Zafar, Armand Perret-Liaudet, Caroline Lacroux, Séverine Lugan, Naima Aron, Herve Cassard, Claudia Ponto, Fabien Corbière, Juan Maria Torres, Inga Zerr, and Olivier AndreolettiComments to Author 
Author affiliations: Institut National de la Recherche Agronomique/Ecole Nationale Vétérinaire, Toulouse, France (J.Y. Douet, C. Lacroux, S. Lugan, N. Aron, H. Cassard, F. Corbière, O. Andréoletti); National Reference Center for Transmissible Spongiform Encephalopathy, Georg August University, Göttingen, Germany (S. Zafar, C. Ponto, I. Zerr); Hospices Civils de Lyon, France (A. Perret-Liaudet); BioRan, Bron, France (A. Perret-Liaudet); Centro de Investigación en Sanidad Animal, Madrid, Spain (J.M. Torres)

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Table 1

Titration of sCJD and vCJD isolates in transgenic mice expressing the human or bovine prion protein*†

Dilution sCJD MM1 in tgHu

vCJD in tgBov
Positive transmission in mice Incubation period, d Positive transmission in mice Incubation period, d
Not diluted 6/6 186 ± 10 6/6 249 ± 2
10−1 6/6 213 ± 15 6/6 283 ± 15
10−2 6/6 240 ± 13 6/6 316 ± 21
10−3 6/6 263 ± 24 6/6 342 ± 10
10-4- 6/6 296 ± 26 6/6 453 ± 66
10−5 6/6 323 ± 29 4/6 499 ± 17
10−6 1/6 316 1/6 502
10−7 0/6 >650 0/6 >700
Infectious titer, ID50/g of brain (95% CI) 106.67 (106.33−106.97) 106.33 (105,84 −106.82)

*sCJD, sporadic Creutzfeld-Jakob Disease; tgHu, human PrP gene ;PrP, protease-resistant prion protein; vCJD, variant CJD; tgBov transgenic mice overexpressing bovine PrP, ID, infectious dose.
†Successive 1/10 dilutions of 10% brain homogenate (frontal cortex) from patients affected by vCJD and sCJD were injected intracerebrally to tgHu (n = 6) and tgBov (n = 6) mice, respectively. Those 2 patients were different from the 1 whose blood was tested in bioassay (Table 2). Mice were euthanized when they showed clinical signs of infection or after 650 days postinfection. Mice were considered infected when abnormal prion protein deposition was detected in the brain by western blot by using Sha31 monoclonal antibody, which recognizes amino acids 145–152 (YEDRYYRE) of the sheep prion protein. Infectious titers were estimated by the Spearman-Karber method (14).

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