1887

Abstract

Prions, infectious agents causing transmissible spongiform encephalopathy (TSE), are composed primarily of the pathogenic form (PrP) of the host-encoded prion protein. Although very low levels of infectivity have been detected in urine from scrapie-infected rodents, no reports of urinary PrP have been substantiated. Studies on the dynamics of urinary PrP during infection are needed to ensure the safety of urine-derived biopharmaceuticals and to assess the possible horizontal transmission of prion diseases. Using the protein misfolding cyclic amplification technique, a time-course study of urinary excretion and blood levels of PrP was performed in Sc237-infected hamsters and a high rate of PrP excretion was found during the terminal stage of the disease. Following oral administration, PrP was present in all buffy coat samples examined; it was also present in most of the plasma samples obtained from hamsters in the symptomatic stage. PrP was excreted in urine for a few days after oral administration; subsequently, urinary PrP was not detected until the terminal disease stage. These results represent the first biochemical detection of PrP in urine from TSE-infected animals.

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2007-10-01
2019-11-17
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References

  1. Arthur, W. J. & Alldredge, A. W. ( 1979; ). Soil ingestion by mule deer in northcentral Colorado. J Range Manage 32, 67–71.[CrossRef]
    [Google Scholar]
  2. Asante, E. A., Linehan, J. M., Gowland, I., Joiner, S., Fox, K., Cooper, S., Osiguwa, O., Gorry, M., Welch, J. & other authors ( 2006; ). Dissociation of pathological and molecular phenotype of variant Creutzfeldt–Jakob disease in transgenic human prion protein 129 heterozygous mice. Proc Natl Acad Sci U S A 103, 10759–10764.[CrossRef]
    [Google Scholar]
  3. Aucouturier, P., Geissmann, F., Damotte, D., Saborio, G. P., Meeker, H. C., Kascsak, R., Kascsak, R., Carp, R. I. & Wisniewski, T. ( 2001; ). Infected splenic cells are sufficient for prion transmission to the CNS in mouse scrapie. J Clin Invest 108, 703–708.[CrossRef]
    [Google Scholar]
  4. Brown, P. & Gajdusek, D. C. ( 1991; ). Survival of scrapie virus after 3 years' internment. Lancet 337, 269–270.[CrossRef]
    [Google Scholar]
  5. Castilla, J., Saá, P., Hetz, C. & Soto, C. ( 2005a; ). In vitro generation of infectious scrapie prions. Cell 121, 195–206.[CrossRef]
    [Google Scholar]
  6. Castilla, J., Saá, P. & Soto, C. ( 2005b; ). Detection of prions in blood. Nat Med 11, 982–985.
    [Google Scholar]
  7. Caughey, B. W., Dong, A., Bhat, K. S., Ernst, D., Hayes, S. F. & Caughey, F. S. ( 1991; ). Secondary structure analysis of the scrapie-associated protein PrP27–30 in water by infrared spectroscopy. Biochemistry 30, 7672–7680.[CrossRef]
    [Google Scholar]
  8. Cervenakova, L., Yakovleva, O., McKenzie, C., Kolchinsky, S., McShane, L., Drohan, W. N. & Brown, P. ( 2003; ). Similar levels of infectivity in the blood of mice infected with human-derived vCJD and GSS strains of transmissible spongiform encephalopathy. Transfusion 43, 1687–1694.[CrossRef]
    [Google Scholar]
  9. Fischer, M. B., Roeckl, C., Parizek, P., Schwarz, H. P. & Aguzzi, A. ( 2000; ). Binding of disease-associated prion protein to plasminogen. Nature 408, 479–483.[CrossRef]
    [Google Scholar]
  10. Furukawa, H., Doh-ura, K., Okuwaki, R., Shirabe, S., Yamamoto, K., Udono, H., Ito, T., Katamine, S. & Niwa, M. ( 2004; ). A pitfall in diagnosis of human prion diseases using detection of protease-resistant prion protein in urine. Contamination with bacterial outer membrane proteins. J Biol Chem 279, 23661–23667.[CrossRef]
    [Google Scholar]
  11. Head, M. W., Kouverianou, E., Taylor, L., Green, A. & Knight, R. ( 2005; ). Evaluation of urinary PrPSc as a diagnostic test for sporadic, variant, and familial CJD. Neurology 64, 1794–1796.[CrossRef]
    [Google Scholar]
  12. Holada, K., Vostal, J. G., Theisen, P. W., MacAuley, C., Gregori, L. & Rohwer, R. G. ( 2002; ). Scrapie infectivity in hamster blood is not associated with platelets. J Virol 76, 4649–4650.[CrossRef]
    [Google Scholar]
  13. Houston, F., Foster, J. D., Chong, A., Hunter, N. & Bostock, C. J. ( 2000; ). Transmission of BSE by blood transfusion in sheep. Lancet 356, 999–1000.[CrossRef]
    [Google Scholar]
  14. Huang, F.-P., Farquhar, C. F., Mabbott, N. A., Bruce, M. E. & MacPherson, G.G. ( 2002; ). Migrating intestinal dendritic cells transport PrPSc from the gut. J Gen Virol 83, 267–271.
    [Google Scholar]
  15. Hunter, N., Foster, J., Chong, A., McCutcheon, S., Parnham, D., Eaton, S., MacKenzie, C. & Houston, F. ( 2002; ). Transmission of prion diseases by blood transfusion. J Gen Virol 83, 2897–2905.
    [Google Scholar]
  16. Johnson, C. J., Phillips, K. E., Schramm, P. T., McKenzie, D., Aiken, J. M. & Pedersen, J. A. ( 2006; ). Prions adhere to soil minerals and remain infectious. PLoS Pathog 2, e32 [CrossRef]
    [Google Scholar]
  17. Kariv-Inbal, Z., Ben-Hur, T., Grigoriadis, N. C., Engelstein, R. & Gabizon, R. ( 2006; ). Urine from scrapie-infected hamsters comprises low levels of prion infectivity. Neurodegener Dis 3, 123–128.[CrossRef]
    [Google Scholar]
  18. Leita, L., Fornasier, F., De Nobili, M., Bertoli, A., Genovesi, S. & Sequi, P. ( 2006; ). Interaction of prion proteins with soil. Soil Biol Biochem 38, 1638–1644.[CrossRef]
    [Google Scholar]
  19. Mathiason, C. K., Powers, J. G., Dahmes, S. J., Osborn, D. A., Miller, K. V., Warren, R. J., Mason, G. L., Hays, S. A., Hayes-Klug, J. & other authors ( 2006; ). Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314, 133–136.[CrossRef]
    [Google Scholar]
  20. Miller, M. W., Wild, M. A. & Williams, E. S. ( 1998; ). Epidemiology of chronic wasting disease in captive Rocky Mountain elk. J Wildl Dis 34, 532–538.[CrossRef]
    [Google Scholar]
  21. Miller, M. W., Williams, E. S., McCarty, C. W., Spraker, T. R., Kreeger, T. J., Larsen, C. T. & Thorne, E. T. ( 2000; ). Epizootiology of chronic wasting disease in free-ranging cervids in Colorado and Wyoming. J Wildl Dis 36, 676–690.[CrossRef]
    [Google Scholar]
  22. Murayama, Y., Yoshioka, M., Horii, H., Takata, M., Yokoyama, T., Sudo, T., Sato, K., Shinagawa, M. & Mohri, S. ( 2006; ). Protein misfolding cyclic amplification as a rapid test for assessment of prion inactivation. Biochem Biophys Res Commun 348, 758–762.[CrossRef]
    [Google Scholar]
  23. Pan, K. M., Baldwin, M., Nguyen, J., Gasset, M., Serban, A., Groth, D., Mehlhorn, I., Huang, Z., Fletterick, R. J. & other authors ( 1993; ). Conversion of α-helices into β-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci U S A 90, 10962–10966.[CrossRef]
    [Google Scholar]
  24. Prusiner, S. B. ( 1991; ). Molecular biology of prion diseases. Science 252, 1515–1522.[CrossRef]
    [Google Scholar]
  25. Prusiner, S. B. ( 1998; ). Prions. Proc Natl Acad Sci U S A 95, 13363–13383.[CrossRef]
    [Google Scholar]
  26. Race, R. E., Priola, S. A., Bessen, R. A., Ernst, D., Dockter, J., Rall, G. F., Mucke, L., Chesebro, B. & Oldstone, M. B. ( 1995; ). Neuron-specific expression of a hamster prion protein minigene in transgenic mice induces susceptibility to hamster scrapie agent. Neuron 15, 1183–1191.[CrossRef]
    [Google Scholar]
  27. Saá, P., Castilla, J. & Soto, C. ( 2006a; ). Ultra-efficient replication of infectious prions by automated protein misfolding cyclic amplification. J Biol Chem 281, 35245–35252.[CrossRef]
    [Google Scholar]
  28. Saá, P., Castilla, J. & Soto, C. ( 2006b; ). Presymptomatic detection of prions in blood. Science 313, 92–94.[CrossRef]
    [Google Scholar]
  29. Saborio, G. P., Permanne, B. & Soto, C. ( 2001; ). Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411, 810–813.[CrossRef]
    [Google Scholar]
  30. Seeger, H., Heikenwalder, M., Zeller, N., Kranich, J., Schwarz, P., Gaspert, A., Seifert, B., Miele, G. & Aguzzi, A. ( 2005; ). Coincident scrapie infection and nephritis lead to urinary prion excretion. Science 310, 324–326.[CrossRef]
    [Google Scholar]
  31. Serban, A., Legname, G., Hansen, K., Kovaleva, N. & Prusiner, S. B. ( 2004; ). Immunoglobulins in urine of hamsters with scrapie. J Biol Chem 279, 48817–48820.[CrossRef]
    [Google Scholar]
  32. Shaked, G. M., Shaked, Y., Kariv-Inbal, Z., Halimi, M., Avraham, I. & Gabizon, R. ( 2001; ). A protease-resistant prion protein isoform is present in urine of animals and humans affected with prion diseases. J Biol Chem 276, 31479–31482.[CrossRef]
    [Google Scholar]
  33. Soos, T. J., Sims, T. N., Barisoni, L., Lin, K., Littman, D. R., Dustin, M. L. & Nelson, P. J. ( 2006; ). CX3CR1+ interstitial dendritic cells form a contiguous network throughout the entire kidney. Kidney Int 70, 591–596.
    [Google Scholar]
  34. Taylor, D. M., Brown, J. M., Fernie, K. & McConnell, I. ( 1997; ). The effect of formic acid on BSE and scrapie infectivity in fixed and unfixed brain-tissue. Vet Microbiol 58, 167–174.[CrossRef]
    [Google Scholar]
  35. Taylor, D. M., Fernie, K., Reichl, H. E. & Somerville, R. A. ( 2000; ). Infectivity in the blood of mice with a BSE-derived agent. J Hosp Infect 46, 78–79.[CrossRef]
    [Google Scholar]
  36. Williams, E. S. ( 2005; ). Chronic wasting disease. Vet Pathol 42, 530–549.[CrossRef]
    [Google Scholar]
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