1887

Journal of General Virology header logo

Volume 86, Issue 5

Expression of PrP on cellular components of sheep blood Free

Abstract

PrP, a glycosylphosphatidylinositol-linked glycoprotein, plays a central role in the pathogenesis of transmissible spongiform encephalopathies (TSEs), undergoing a conformational alteration to the disease-associated isoform, commonly designated PrP. PrP is expressed in many tissues other than the nervous system, although its precise function(s) remains unclear. It has previously been demonstrated that TSEs can be transmitted by blood transfusion in sheep. The aim of this work was to identify which components of blood carried the infection. As an initial step, the distribution of PrP on cellular components of sheep blood was examined to identify potential targets for infection. Cell-surface expression of PrP was found only on peripheral blood mononuclear cells (PBMCs); however, platelets also contained significant amounts of intracellular PrP. The level of PrP expressed on the cell surface of PBMCs was influenced by PrP genotype, with the highest levels found in scrapie-susceptible VRQ/VRQ sheep and the lowest levels in scrapie-resistant ARR/ARR sheep. In susceptible sheep, PrP was expressed at varying levels on all major subsets of PBMCs, with the highest levels on the CD21 subset of B cells, and PrP expression was upregulated dramatically on CD21 B cells in some scrapie-infected sheep.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80561-0
2005-05-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/5/vir861571.html?itemId=/content/journal/jgv/10.1099/vir.0.80561-0&mimeType=html&fmt=ahah

References

  1. Barclay G. R., Hope J., Birkett C. R., Turner M. L. 1999; Distribution of cell-associated prion protein in normal adult blood determined by flow cytometry. Br J Haematol 107:804–814 [CrossRef]
     [Google Scholar]
  2. Barclay G. R., Houston E. F., Halliday S. I., Farquhar C. F., Turner M. L. 2002; Comparative analysis of normal prion protein expression on human, rodent, and ruminant blood cells by using a panel of prion antibodies. Transfusion 42:517–526 [CrossRef]
     [Google Scholar]
  3. Bembridge G. P., Howard C. J., Parsons K. R., Sopp P. 1993; Identification of monoclonal antibodies specific for bovine leukocyte common antigen (CD45) together with a novel broadly expressed leukocyte differentiation antigen, BoWC11. Vet Immunol Immunopathol 39:115–120 [CrossRef]
     [Google Scholar]
  4. Bendheim P. E., Brown H. R., Rudelli R. D., Scala L. J., Goller N. L., Wen G. Y., Kascsak R. J., Cashman N. R., Bolton D. C. 1992; Nearly ubiquitous tissue distribution of the scrapie agent precursor protein. Neurology 42:149–156 [CrossRef]
     [Google Scholar]
  5. Blättler T., Brandner S., Raeber A. J., Klein M. A., Voigtländer T., Weissmann C., Aguzzi A. 1997; PrP-expressing tissue required for transfer of scrapie infectivity from spleen to brain. Nature 389:69–73 [CrossRef]
     [Google Scholar]
  6. Bolton D. C., McKinley M. P., Prusiner S. B. 1982; Identification of a protein that purifies with the scrapie prion. Science 218:1309–1311 [CrossRef]
     [Google Scholar]
  7. Brown P. 1995; Can Creutzfeldt-Jakob disease be transmitted by transfusion?. Curr Opin Hematol 2:472–477 [CrossRef]
     [Google Scholar]
  8. Brown P., Rohwer R. G., Dunstan B. C., MacAuley C., Gajdusek D. C., Drohan W. N. 1998; The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy. Transfusion 38:810–816 [CrossRef]
     [Google Scholar]
  9. Brown P., Cervenakova L., McShane L. M., Barber P., Rubenstein R., Drohan W. N. 1999; 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 39:1169–1178 [CrossRef]
     [Google Scholar]
  10. Bruce M. E., Brown K. L., Mabbott N. A., Farquhar C. F., Jeffrey M. 2000; Follicular dendritic cells in TSE pathogenesis. Immunol Today 21:442–446 [CrossRef]
     [Google Scholar]
  11. Cashman N. R., Loertscher R., Nalbantoglu J., Shaw I., Kascsak R. J., Bolton D. C., Bendheim P. E. 1990; Cellular isoform of the scrapie agent protein participates in lymphocyte activation. Cell 61:185–192 [CrossRef]
     [Google Scholar]
  12. Eklund C. M., Kennedy R. C., Hadlow W. J. 1967; Pathogenesis of scrapie virus infection in the mouse. J Infect Dis 117:15–22 [CrossRef]
     [Google Scholar]
  13. Gupta V. K., McConnell I., Dalziel R. G., Hopkins J. 1998; Two B cell subpopulations have distinct recirculation characteristics. Eur J Immunol 28:1597–1603 [CrossRef]
     [Google Scholar]
  14. Hadlow W. J., Kennedy R. C., Race R. E. 1982; Natural infection of Suffolk sheep with scrapie virus. J Infect Dis 146:657–664 [CrossRef]
     [Google Scholar]
  15. Hall G. A., Sopp P., Howard C. J. 1993; An investigation of temporary workshop clusters reacting with cells of the mononuclear phagocytic system. Vet Immunol Immunopathol 39:225–236 [CrossRef]
     [Google Scholar]
  16. Herrmann L. M., Davis W. C., Knowles D. P., Wardrop K. J., Sy M. S., Gambetti P., O'Rourke K. I. 2001; Cellular prion protein is expressed on peripheral blood mononuclear cells but not platelets of normal and scrapie-infected sheep. Haematologica 86:146–153
     [Google Scholar]
  17. Herrmann L. M., Baszler T. V., Knowles D. P., Cheevers W. P. 2002; PrPSc is not detected in peripheral blood leukocytes of scrapie-infected sheep: determining the limit of sensitivity by immunohistochemistry. Clin Diagn Lab Immunol 9:499–502
     [Google Scholar]
  18. Hill A. F., Butterworth R. J., Joiner S. 12 other authors 1999; Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 353:183–189 [CrossRef]
     [Google Scholar]
  19. Holada K., Vostal J. G. 2000; Different levels of prion protein (PrPc) expression on hamster, mouse and human blood cells. Br J Haematol 110:472–480 [CrossRef]
     [Google Scholar]
  20. Holada K., Mondoro T. H., Muller J., Vostal J. G. 1998; Increased expression of phosphatidylinositol-specific phospholipase C resistant prion proteins on the surface of activated platelets. Br J Haematol 103:276–282 [CrossRef]
     [Google Scholar]
  21. 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]
  22. 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]
  23. Houston E. F., Halliday S. I., Jeffrey M., Goldmann W., Hunter N. 2002; New Zealand sheep with scrapie-susceptible PrP genotypes succumb to experimental challenge with a sheep-passaged scrapie isolate (SSBP/1. J Gen Virol 83:1247–1250
     [Google Scholar]
  24. Howard C. J., Sopp P., Parsons K. R. 1992; L-selectin expression differentiates T cells isolated from different lymphoid tissues in cattle but does not correlate with memory. Immunology 77:228–234
     [Google Scholar]
  25. 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]
  26. Korth C., Stierli B., Streit P. 14 other authors 1997; Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 390:74–77 [CrossRef]
     [Google Scholar]
  27. Krasemann S., Jurgens T., Bodemer W. 1999; Generation of monoclonal antibodies against prion proteins with an unconventional nucleic acid-based immunization strategy. J Biotechnol 73:119–129 [CrossRef]
     [Google Scholar]
  28. Llewelyn C. A., Hewitt P. E., Knight R. S. G., Amar K., Cousens S., Mackenzie J., Will R. G. 2004; Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 363:417–421 [CrossRef]
     [Google Scholar]
  29. Mabbott N. A., Brown K. L., Manson J., Bruce M. E. 1997; T-lymphocyte activation and the cellular form of the prion protein. Immunology 92:161–165 [CrossRef]
     [Google Scholar]
  30. MacGregor I., Hope J., Barnard G. 8 other authors 1999; Application of a time-resolved fluoroimmunoassay for the analysis of normal prion protein in human blood and its components. Vox Sang 77:88–96 [CrossRef]
     [Google Scholar]
  31. MacHugh N. D., Sopp P. 1991; Individual antigens of cattle. Bovine CD8 (BoCD8). Vet Immunol Immunopathol 27:65–69 [CrossRef]
     [Google Scholar]
  32. Mackay C. R., Beya M. F., Matzinger P. 1989; Gamma/delta T cells express a unique surface molecule appearing late during thymic development. Eur J Immunol 19:1477–1483 [CrossRef]
     [Google Scholar]
  33. Maddox J. F., Mackay C. R., Brandon M. R. 1985; Surface antigens, SBU-T4 and SBU-T8, of sheep T lymphocyte subsets defined by monoclonal antibodies. Immunology 55:739–748
     [Google Scholar]
  34. Maddox J. F., Mackay C. R., Brandon M. R. 1987; Ontogeny of ovine lymphocytes. II. An immunohistological study on the development of T lymphocytes in the sheep fetal spleen. Immunology 62:107–112
     [Google Scholar]
  35. Mateo A., Pintado C. O., Perez de la Lastra J., Dusinsky R., Simon M., Naessens J., Llanes D. 1996; Ruminant cluster CD41/CD61. Vet Immunol Immunopathol 52:251–253 [CrossRef]
     [Google Scholar]
  36. Peden A. H., Head M. W., Ritchie D. L., Bell J. E., Ironside J. W. 2004; Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 364:527–529 [CrossRef]
     [Google Scholar]
  37. Perini F., Vidal R., Ghetti B., Tagliavini F., Frangione B., Prelli F. 1996; PrP27–30 is a normal soluble prion protein fragment released by human platelets. Biochem Biophys Res Commun 223:572–577 [CrossRef]
     [Google Scholar]
  38. Prusiner S. B. 1998; Prions. Proc Natl Acad Sci U S A 95:13363–13383 [CrossRef]
     [Google Scholar]
  39. Rezaei H., Choiset Y., Eghiaian F., Treguer E., Mentre P., Debey P., Grosclaude J., Haertle T. 2002; Amyloidogenic unfolding intermediates differentiate sheep prion protein variants. J Mol Biol 322:799–814 [CrossRef]
     [Google Scholar]
  40. Schmerr M. J., Jenny A. L., Bulgin M. S., Miller J. M., Hamir A. N., Cutlip R. C., Goodwin K. R. 1999; Use of capillary electrophoresis and fluorescent labeled peptides to detect the abnormal prion protein in the blood of animals that are infected with a transmissible spongiform encephalopathy. J Chromatogr A 853:207–214 [CrossRef]
     [Google Scholar]
  41. Sopp P. 1996; Ruminant cluster CD21. Vet Immunol Immunopathol 52:249 [CrossRef]
     [Google Scholar]
  42. Sopp P., Howard C. J. 1997; Cross-reactivity of monoclonal antibodies to defined human leucocyte differentiation antigens with bovine cells. Vet Immunol Immunopathol 56:11–25 [CrossRef]
     [Google Scholar]
  43. Sopp P., Kwong L. S., Howard C. J. 1996; Identification of bovine CD14. Vet Immunol Immunopathol 52:323–328 [CrossRef]
     [Google Scholar]
  44. Tenzer S., Stoltze L., Schönfisch B., Dengjel J., Müller M., Stevanović S., Rammensee H.-G., Schild H. 2004; Quantitative analysis of prion-protein degradation by constitutive and immuno-20S proteasomes indicates differences correlated with disease susceptibility. J Immunol 172:1083–1091 [CrossRef]
     [Google Scholar]
  45. Thackray A. M., Yang S., Wong E., Fitzmaurice T. J., Morgan-Warren R. J., Bujdoso R. 2004; Conformational variation between allelic variants of cell-surface ovine prion protein. Biochem J 381:221–229 [CrossRef]
     [Google Scholar]
  46. Wadsworth J. D. F., Joiner S., Hill A. F., Campbell T. A., Desbruslais M., Luthert P. J., Collinge J. 2001; Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet 358:171–180 [CrossRef]
     [Google Scholar]
  47. Young A. J., Marston W. L., Dessing M., Dudler L., Hein W. R. 1997; Distinct recirculating and non-recirculating B-lymphocyte pools in the peripheral blood are defined by coordinated expression of CD21 and L-selectin. Blood 90:4865–4875
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80561-0
Loading
Expression of PrPC on cellular components of sheep blood
J. Gen. Virol. 86, 1571 (2005); https://doi.org/10.1099/vir.0.80561-0
/content/journal/jgv/10.1099/vir.0.80561-0
/content/journal/jgv/10.1099/vir.0.80561-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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