This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thackray, A. M.
Right arrow Articles by Bujdoso, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thackray, A. M.
Right arrow Articles by Bujdoso, R.

 Previous Article  |  Next Article 

Journal of Virology, March 2002, p. 2510-2517, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2510-2517.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Chronic Subclinical Prion Disease Induced by Low-Dose Inoculum

*** Alana M. Thackray,1 Michael A. Klein,2 Adriano Aguzzi,3 and Raymond Bujdoso1*

Centre for Veterinary Science, Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom,1 University Hospital Basel, Institute of Pathology, CH-4003 Basel,2 Institute of Neuropathology, University Hospital of Zürich, CH-8091 Zürich, Switzerland3

Received 24 September 2001/ Accepted 16 November 2001

We have compared the transmission characteristics of the two mouse-adapted scrapie isolates, ME7 and Rocky Mountain Laboratory (RML), in tga20 mice. These mice express elevated levels of PrP protein compared to wild-type mice and display a relatively short disease incubation period following intracerebral prion inoculation. Terminal prion disease in tga20 mice induced by ME7 or RML was characterized by a distinct pattern of clinical signs and different incubation times. High-dose RML inoculated intracerebrally into tga20 mice induced the most rapid onset of clinical signs, with mice succumbing to terminal disease after only 58 ± 3 days. In contrast, high-dose ME7 gave a mean time to terminal disease of 74 ± 0 days. Histological examination of brain sections from prion-inoculated tga20 mice at terminal disease showed that ME7 gave rise to a more general and extensive pattern of vacuolation than RML. Low-dose inoculum failed to induce terminal disease but did cause preclinical symptoms, including the appearance of reversible clinical signs. Some mice oscillated between showing no clinical signs and early clinical signs for many months but never progressed to terminal disease. Brain tissue from these mice with chronic subclinical prion disease, sacrificed at >200 days postinoculation, contained high levels of infectivity and showed the presence of PrPSc. Parallel analysis of brain tissue from mice with terminal disease showed similar levels of infectivity and detectable PrPSc. These results show that high levels of infectivity and the presence of the abnormal isomer of PrP can be detected in mice with subclinical disease following low-dose prion inoculation.

* Corresponding author. Mailing address: Centre for Veterinary Science, Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Rd., Cambridge CB3 0ES, United Kingdom. Phone: 44-1223-337655. Fax: 44-1223-337610. E-mail: rb202{at}cam.ac.uk.

Journal of Virology, March 2002, p. 2510-2517, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2510-2517.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Collinge, J., Whitfield, J., McKintosh, E., Frosh, A., Mead, S., Hill, A. F, Brandner, S., Thomas, D., Alpers, M. P (2008). A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea. Phil Trans R Soc B 363: 3725-3739 [Abstract] [Full Text]  
  • Thackray, A. M., Hopkins, L., Spiropoulos, J., Bujdoso, R. (2008). Molecular and Transmission Characteristics of Primary-Passaged Ovine Scrapie Isolates in Conventional and Ovine PrP Transgenic Mice. J. Virol. 82: 11197-11207 [Abstract] [Full Text]  
  • Thackray, A. M., Hopkins, L., Klein, M. A., Bujdoso, R. (2007). Mouse-Adapted Ovine Scrapie Prion Strains Are Characterized by Different Conformers of PrPSc. J. Virol. 81: 12119-12127 [Abstract] [Full Text]  
  • Deleault, N. R., Harris, B. T., Rees, J. R., Supattapone, S. (2007). From the Cover: Formation of native prions from minimal components in vitro. Proc. Natl. Acad. Sci. USA 104: 9741-9746 [Abstract] [Full Text]  
  • Wells, G. A. H., Konold, T., Arnold, M. E., Austin, A. R., Hawkins, S. A. C., Stack, M., Simmons, M. M., Lee, Y. H., Gavier-Widen, D., Dawson, M., Wilesmith, J. W. (2007). Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle. J. Gen. Virol. 88: 1363-1373 [Abstract] [Full Text]  
  • Lezmi, S., Bencsik, A., Baron, T. (2006). PET-blot Analysis Contributes to BSE Strain Recognition in C57Bl/6 Mice. J. Histochem. Cytochem. 54: 1087-1094 [Abstract] [Full Text]  
  • Jacquemot, C., Cuche, C., Dormont, D., Lazarini, F. (2005). High Incidence of Scrapie Induced by Repeated Injections of Subinfectious Prion Doses. J. Virol. 79: 8904-8908 [Abstract] [Full Text]  
  • Thackray, A. M., McKenzie, A. N., Klein, M. A., Lauder, A., Bujdoso, R. (2004). Accelerated Prion Disease in the Absence of Interleukin-10. J. Virol. 78: 13697-13707 [Abstract] [Full Text]  
  • Xiang, W., Windl, O., Wunsch, G., Dugas, M., Kohlmann, A., Dierkes, N., Westner, I. M., Kretzschmar, H. A. (2004). Identification of Differentially Expressed Genes in Scrapie-Infected Mouse Brains by Using Global Gene Expression Technology. J. Virol. 78: 11051-11060 [Abstract] [Full Text]  
  • Thackray, A. M., Klein, M. A., Bujdoso, R. (2003). Subclinical Prion Disease Induced by Oral Inoculation. J. Virol. 77: 7991-7998 [Abstract] [Full Text]  
  • Baier, M., Norley, S., Schultz, J., Burwinkel, M., Schwarz, A., Riemer, C. (2003). Prion diseases: infectious and lethal doses following oral challenge. J. Gen. Virol. 84: 1927-1929 [Abstract] [Full Text]  
  • Weissmann, C, Flechsig, E (2003). PrP knock-out and PrP transgenic mice in prion research. Br Med Bull 66: 43-60 [Abstract] [Full Text]  
  • Hill, A. F, Collinge, J. (2003). Subclinical prion infection in humans and animals. Br Med Bull 66: 161-170 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»