Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 20, Number 1—January 2014
Dispatch

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)

Main Article

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).

Main Article

References
  1. Parchi  P, Castellani  R, Capellari  S, Ghetti  B, Young  K, Chen  SG, Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol. 1996;39:767–78. DOIPubMedGoogle Scholar
  2. Brown  P, Brandel  JP, Sato  T, Nakamura  Y, MacKenzie  J, Will  RG, Iatrogenic Creutzfeldt-Jakob disease, final assessment. Emerg Infect Dis. 2012;18:901–7. DOIPubMedGoogle Scholar
  3. Brown  P, Cervenakova  L, Diringer  H. Blood infectivity and the prospects for a diagnostic screening test in Creutzfeldt-Jakob disease. J Lab Clin Med. 2001;137:5–13. DOIPubMedGoogle Scholar
  4. Brown  P, Gibbs  CJ Jr, Rodgers-Johnson  P, Asher  DM, Sulima  MP, Bacote  A, Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol. 1994;35:513–29 . DOIPubMedGoogle Scholar
  5. Bruce  ME, Will  RG, Ironside  JW, McConnell  I, Drummond  D, Suttie  A, Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature. 1997;389:498–501. DOIPubMedGoogle Scholar
  6. Peden  AH, Head  MW, Ritchie  DL, Bell  JE, Ironside  JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet. 2004;364:527–9. DOIPubMedGoogle Scholar
  7. Peden  A, McCardle  L, Head  MW, Love  S, Ward  HJ, Cousens  SN, Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia. Haemophilia. 2010;16:296–304. DOIPubMedGoogle Scholar
  8. Bruce  ME, McConnell  I, Will  RG, Ironside  JW. Detection of variant Creutzfeldt-Jakob disease infectivity in extraneural tissues. Lancet. 2001;358:208–9. DOIPubMedGoogle Scholar
  9. Andréoletti  O, Litaise  C, Simmons  H, Corbiere  F, Lugan  S, Costes  P, Highly efficient prion transmission by blood transfusion. PLoS Pathog. 2012;8:e1002782. DOIPubMedGoogle Scholar
  10. Béringue  V, Vilotte  JL, Laude  H. Prion agent diversity and species barrier. Vet Res. 2008;39:47. DOIPubMedGoogle Scholar
  11. Castilla  J, Gutiérrez Adán  A, Brun  A, Pintado  B, Ramirez  MA, Parra  B, Early detection of PrPres in BSE-infected bovine PrP transgenic mice. Arch Virol. 2003;148:677–91. DOIPubMedGoogle Scholar
  12. Padilla  D, Beringue  V, Espinosa  JC, Andreoletti  O, Jaumain  E, Reine  F, Sheep and goat BSE propagate more efficiently than cattle BSE in human PrP transgenic mice. PLoS Pathog. 2011;7:e1001319. DOIPubMedGoogle Scholar
  13. Markus  RA, Frank  J, Groshen  S, Azen  SP. An alternative approach to the optimal design of an LD50 bioassay. Stat Med. 1995;14:841–52 . DOIPubMedGoogle Scholar
  14. Brown  P, Cervenakova  L, McShane  LM, Barber  P, Rubenstein  R, Drohan  WN. Further studies of blood infectivity in an experimental model of transmissible spongiform encephalopathy, with an explanation of why blood components do not transmit Creutzfeldt-Jakob disease in humans. Transfusion. 1999;39:1169–78. DOIPubMedGoogle Scholar

Main Article

Page created: January 03, 2014
Page updated: January 03, 2014
Page reviewed: January 03, 2014
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external