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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82786-0
2007-10-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/10/2890.html?itemId=/content/journal/jgv/10.1099/vir.0.82786-0&mimeType=html&fmt=ahah

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]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82786-0
Loading
/content/journal/jgv/10.1099/vir.0.82786-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error