1887

Abstract

Many studies have demonstrated prion infectivity in whole blood and blood components in a variety of transmissible spongiform encephalopathies of livestock and rodents, and variant Creutzfeldt–Jakob disease in humans, as well as an association between pathogenic prion protein (PrP) and different immune cells (e.g. follicular dendritic cells, T and B lymphocytes, monocytes and tingible body macrophages). To further investigate the role of various blood components in prion disease transmission, we intracranially inoculated genetically susceptible VRQ/ARQ and ARQ/ARQ sheep with inocula composed of CD11c B1 lymphocytes, CD68 +macrophages, or platelet-rich plasma derived from clinically ill sheep infected with the US no. 13–7 scrapie agent. At the completion of the study, we found that VRQ/ARQ and ARQ/ARQ sheep inoculated with CD11c B1 lymphocytes and CD68 macrophages developed scrapie with detectable levels of PrP in the central nervous system and lymphoreticular system, while those inoculated with platelet-rich plasma did not develop disease and did not have detectable PrP by immunohistochemistry or enzyme immunoassay. This study complements and expands on earlier findings that white blood cells harbour prion infectivity, and reports CD11c B1 lymphocytes and CD68 macrophages as additional targets for possible preclinical detection of prion infection in blood.

Loading

Article metrics loading...

/content/journal/acmi/10.1099/acmi.0.000155
2020-07-28
2020-10-22
Loading full text...

Full text loading...

/deliver/fulltext/acmi/2/9/acmi000155.html?itemId=/content/journal/acmi/10.1099/acmi.0.000155&mimeType=html&fmt=ahah

References

  1. Heggebø R, Press CM, Gunnes G, Inge Lie K, Tranulis MA et al. Distribution of prion protein in the ileal Peyer's patch of scrapie-free lambs and lambs naturally and experimentally exposed to the scrapie agent. J Gen Virol 2000; 81:2327–2337 [CrossRef][PubMed]
    [Google Scholar]
  2. Jeffrey M, González L, Espenes A, Press CM, Martin S et al. Transportation of prion protein across the intestinal mucosa of scrapie-susceptible and scrapie-resistant sheep. J Pathol 2006; 209:4–14 [CrossRef][PubMed]
    [Google Scholar]
  3. Andréoletti O, Berthon P, Marc D, Sarradin P, Grosclaude J et al. Early accumulation of PrP(Sc) in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. J Gen Virol 2000; 81:3115–3126 [CrossRef][PubMed]
    [Google Scholar]
  4. Muramatsu Y, Onodera A, Horiuchi M, Ishiguro N, Shinagawa M. Detection of PrPSc in sheep at the preclinical stage of scrapie and its significance for diagnosis of insidious infection. Arch Virol 1994; 134:427–432 [CrossRef][PubMed]
    [Google Scholar]
  5. Race R, Ernst D, Jenny A, Taylor W, Sutton D et al. Diagnostic implications of detection of proteinase K-resistant protein in spleen, lymph nodes, and brain of sheep. Am J Vet Res 1992; 53:883–889[PubMed]
    [Google Scholar]
  6. Greenlee JJ, Greenlee MHW. The transmissible spongiform encephalopathies of livestock. Ilar J 2015; 56:7–25 [CrossRef][PubMed]
    [Google Scholar]
  7. Eklund CM, Kennedy RC, Hadlow WJ. Pathogenesis of scrapie virus infection in the mouse. J Infect Dis 1967; 117:15–22 [CrossRef][PubMed]
    [Google Scholar]
  8. Fraser H, Dickinson AG. Pathogenesis of scrapie in the mouse: the role of the spleen. Nature 1970; 226:462–463 [CrossRef][PubMed]
    [Google Scholar]
  9. Jeffrey M, McGovern G, Goodsir CM, Brown KL, Bruce ME. Sites of prion protein accumulation in scrapie-infected mouse spleen revealed by immuno-electron microscopy. J Pathol 2000; 191:323–332 [CrossRef][PubMed]
    [Google Scholar]
  10. Houston F, Foster JD, Chong A, Hunter N, Bostock CJ. Transmission of BSE by blood transfusion in sheep. The Lancet 2000; 356:999–1000 [CrossRef]
    [Google Scholar]
  11. Andréoletti O, Litaise C, Simmons H, Corbière F, Lugan S et al. Highly efficient prion transmission by blood transfusion. PLoS Pathog 2012; 8:e1002782 [CrossRef][PubMed]
    [Google Scholar]
  12. Hunter N, Foster J, Chong A, McCutcheon S, Parnham D et al. Transmission of prion diseases by blood transfusion. J Gen Virol 2002; 83:2897–2905 [CrossRef][PubMed]
    [Google Scholar]
  13. Mathiason CK, Hays SA, Powers J, Hayes-Klug J, Langenberg J et al. Infectious prions in pre-clinical deer and transmission of chronic wasting disease solely by environmental exposure. PLoS One 2009; 4:e5916 [CrossRef][PubMed]
    [Google Scholar]
  14. Holada K, Vostal JG, Theisen PW, MacAuley C, Gregori L et al. Scrapie infectivity in hamster blood is not associated with platelets. J Virol 2002; 76:4649–4650 [CrossRef][PubMed]
    [Google Scholar]
  15. Gregori L, Rohwer RG. Characterization of scrapie-infected and normal hamster blood as an experimental model for TSE-infected human blood. Dev Biol 2007; 127:123–133[PubMed]
    [Google Scholar]
  16. Gregori L, Gurgel PV, Lathrop JT, Edwardson P, Lambert BC et al. Reduction in infectivity of endogenous transmissible spongiform encephalopathies present in blood by adsorption to selective affinity resins. Lancet 2006; 368:2226–2230 [CrossRef][PubMed]
    [Google Scholar]
  17. Gregori L, Lambert BC, Gurgel PV, Gheorghiu L, Edwardson P et al. Reduction of transmissible spongiform encephalopathy infectivity from human red blood cells with prion protein affinity ligands. Transfusion 2006; 46:1152–1161 [CrossRef][PubMed]
    [Google Scholar]
  18. Kuroda Y, Gibbs CJ, Amyx HL, Gajdusek DC. Creutzfeldt-Jakob disease in mice: persistent viremia and preferential replication of virus in low-density lymphocytes. Infect Immun 1983; 41:154–161 [CrossRef][PubMed]
    [Google Scholar]
  19. Manuelidis EE, Kim JH, Mericangas JR, Manuelidis L. Transmission to animals of Creutzfeldt-Jakob disease from human blood. Lancet 1985; 2:896–897 [CrossRef][PubMed]
    [Google Scholar]
  20. Brown P. Can Creutzfeldt-Jakob disease be transmitted by transfusion?. Curr Opin Hematol 1995; 2:472–477 [CrossRef][PubMed]
    [Google Scholar]
  21. Brown P, Rohwer RG, Dunstan BC, MacAuley C, Gajdusek DC et al. The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy. Transfusion 1998; 38:810–816 [CrossRef][PubMed]
    [Google Scholar]
  22. Brown P, Cervenáková L, McShane LM, Barber P, Rubenstein R et al. 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; 39:1169–1178 [CrossRef][PubMed]
    [Google Scholar]
  23. McBride PA, Eikelenboom P, Kraal G, Fraser H, Bruce ME. Prp protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice. J Pathol 1992; 168:413–418 [CrossRef][PubMed]
    [Google Scholar]
  24. Muramoto T, Kitamoto T, Tateishi J, Goto I. The sequential development of abnormal prion protein accumulation in mice with Creutzfeldt-Jakob disease. Am J Pathol 1992; 140:1411[PubMed]
    [Google Scholar]
  25. Sigurdson CJ, Barillas-Mury C, Miller MW, Oesch B, van Keulen LJM et al. PrP(CWD) lymphoid cell targets in early and advanced chronic wasting disease of mule deer. J Gen Virol 2002; 83:2617–2628 [CrossRef][PubMed]
    [Google Scholar]
  26. Mathiason CK, Hayes-Klug J, Hays SA, Powers J, Osborn DA et al. B cells and platelets harbor prion infectivity in the blood of deer infected with chronic wasting disease. J Virol 2010; 84:5097–5107 [CrossRef][PubMed]
    [Google Scholar]
  27. Moore SJ, Smith JD, Greenlee MHW, Nicholson EM, Richt JA et al. Comparison of two us sheep scrapie isolates supports identification as separate strains. Vet Pathol 2016; 53:1187–1196 [CrossRef][PubMed]
    [Google Scholar]
  28. Hamir AN, Kunkle RA, Richt JA, Greenlee JJ, Miller JM. Serial passage of sheep scrapie inoculum in Suffolk sheep. Vet Pathol 2009; 46:39–44 [CrossRef][PubMed]
    [Google Scholar]
  29. Hamir AN, Miller JM, Stack MJ, Chaplin MJ. Failure to detect abnormal prion protein and scrapie-associated fibrils 6 wk after intracerebral inoculation of genetically susceptible sheep with scrapie agent. Can J Vet Res 2002; 66:289[PubMed]
    [Google Scholar]
  30. Spraker TR, O'Rourke KI, Balachandran A, Zink RR, Cummings BA et al. Validation of monoclonal antibody F99/97.6.1 for immunohistochemical staining of brain and tonsil in mule deer (Odocoileus hemionus) with chronic wasting disease. J Vet Diagn Invest 2002; 14:3–7 [CrossRef][PubMed]
    [Google Scholar]
  31. Greenlee JJ, Zhang X, Nicholson EM, Kunkle RA, Hamir AN. Prolonged incubation time in sheep with prion protein containing lysine at position 171. J Vet Diagn Invest 2012; 24:554–558 [CrossRef][PubMed]
    [Google Scholar]
  32. Douet J-Y, Lacroux C, Litaise C, Lugan S, Corbière F et al. Mononucleated blood cell populations display different abilities to transmit prion disease by the transfusion route. J Virol 2016; 90:3439–3445 [CrossRef][PubMed]
    [Google Scholar]
  33. Dassanayake RP, Schneider DA, Truscott TC, Young AJ, Zhuang D et al. Classical scrapie prions in ovine blood are associated with B lymphocytes and platelet-rich plasma. BMC Vet Res 2011; 7:75 [CrossRef][PubMed]
    [Google Scholar]
  34. Dassanayake RP, Madsen-Bouterse SA, Truscott TC, Zhuang D, Mousel MR et al. Classical scrapie prions are associated with peripheral blood monocytes and T-lymphocytes from naturally infected sheep. BMC Vet Res 2016; 12:27 [CrossRef][PubMed]
    [Google Scholar]
  35. Casaccia P, Ladogana A, Xi YG, Pocchiari M. Levels of infectivity in the blood throughout the incubation period of hamsters peripherally injected with scrapie. Arch Virol 1989; 108:145–149 [CrossRef][PubMed]
    [Google Scholar]
  36. Cervenakova L, Yakovleva O, McKenzie C, Kolchinsky S, McShane L et al. Similar levels of infectivity in the blood of mice infected with human-derived vCJD and GSS strains of transmissible spongiform encephalopathy. Transfusion 2003; 43:1687–1694 [CrossRef][PubMed]
    [Google Scholar]
  37. Glatzel M, Abela E, Maissen M, Aguzzi A. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Engl J Med 2003; 349:1812–1820 [CrossRef][PubMed]
    [Google Scholar]
  38. Herzog C, Rivière J, Lescoutra-Etchegaray N, Charbonnier A, Leblanc V et al. Prptse distribution in a primate model of variant, sporadic, and iatrogenic Creutzfeldt-Jakob disease. J Virol 2005; 79:14339–14345 [CrossRef][PubMed]
    [Google Scholar]
  39. Klein MA, Frigg R, Flechsig E, Raeber AJ, Kalinke U et al. A crucial role for B cells in neuroinvasive scrapie. Nature 1997; 390:687690 [CrossRef][PubMed]
    [Google Scholar]
  40. McGovern G, Jeffrey M. Scrapie-specific pathology of sheep lymphoid tissues. PLoS One 2007; 2:e1304 [CrossRef][PubMed]
    [Google Scholar]
  41. Zabel MD, Heikenwalder M, Prinz M, Arrighi I, Schwarz P et al. Stromal complement receptor CD21/35 facilitates lymphoid prion colonization and pathogenesis. J Immunol 2007; 179:6144–6152 [CrossRef][PubMed]
    [Google Scholar]
  42. Mok SWF, Proia RL, Brinkmann V, Mabbott NA. B cell-specific S1PR1 deficiency blocks prion dissemination between secondary lymphoid organs. J Immunol 2012; 188:5032–5040 [CrossRef][PubMed]
    [Google Scholar]
  43. Frigg R, Klein MA, Hegyi I, Zinkernagel RM, Aguzzi A. Scrapie pathogenesis in subclinically infected B-cell-deficient mice. J Virol 1999; 73:9584–9588 [CrossRef][PubMed]
    [Google Scholar]
  44. von Poser-Klein C, Flechsig E, Hoffmann T, Schwarz P, Harms H et al. Alteration of B-cell subsets enhances neuroinvasion in mouse scrapie infection. J Virol 2008; 82:3791–3795 [CrossRef][PubMed]
    [Google Scholar]
  45. Herzenberg LA, Tung JW. B cell lineages: documented at last!. Nat Immunol 2006; 7:225226 [CrossRef][PubMed]
    [Google Scholar]
  46. Gupta VK, McConnell I, Dalziel RG, Hopkins J. Two B cell subpopulations have distinct recirculation characteristics. Eur J Immunol 1998; 28:1597–1603 [CrossRef][PubMed]
    [Google Scholar]
  47. Rhun L. B‐1‐like cells exist in sheep Characterization of their phenotype and behaviour. Immunology. 1998; 95:178–184
    [Google Scholar]
  48. Edwards JC, Moore SJ, Hawthorn JA, Neale MH, Terry LA. PrP(Sc) is associated with B cells in the blood of scrapie-infected sheep. Virology 2010; 405:110–119 [CrossRef][PubMed]
    [Google Scholar]
  49. Young AJ, Marston WL, Dessing M, Dudler L, Hein WR. Distinct recirculating and non-recirculating B-lymphocyte pools in the peripheral blood are defined by coordinated expression of CD21 and L-selectin. Blood 1997; 90:4865–4875 [CrossRef][PubMed]
    [Google Scholar]
  50. Raymond CR, Aucouturier P, Mabbott NA. In vivo depletion of CD11c+ cells impairs scrapie agent neuroinvasion from the intestine. J Immunol 2007; 179:7758–7766 [CrossRef][PubMed]
    [Google Scholar]
  51. Korth C, Stierli B, Streit P, Moser M, Schaller O et al. Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 1997; 390:7477 [CrossRef][PubMed]
    [Google Scholar]
  52. Paramithiotis E, Pinard M, Lawton T, LaBoissiere S, Leathers VL et al. A prion protein epitope selective for the pathologically misfolded conformation. Nat Med 2003; 9:893899 [CrossRef][PubMed]
    [Google Scholar]
  53. Tayebi M, Enever P, Sattar Z, Collinge J, Hawke S. Disease-Associated prion protein elicits immunoglobulin M responses in vivo. Mol Med 2004; 10:104–111 [CrossRef][PubMed]
    [Google Scholar]
  54. Aucouturier P, Geissmann F, Damotte D, Saborio GP, Meeker HC et al. Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie. J Clin Invest 2001; 108:703–708 [CrossRef][PubMed]
    [Google Scholar]
  55. Flores-Langarica A, Sebti Y, Mitchell DA, Sim RB, MacPherson GG. Scrapie pathogenesis: the role of complement C1q in scrapie agent uptake by conventional dendritic cells. J Immunol 2009; 182:1305–1313 [CrossRef][PubMed]
    [Google Scholar]
  56. Huang F-P, Farquhar CF, Mabbott NA, Bruce ME, MacPherson GG. Migrating intestinal dendritic cells transport PrP(Sc) from the gut. J Gen Virol 2002; 83:267–271 [CrossRef][PubMed]
    [Google Scholar]
  57. Luhr KM, Wallin RPA, Ljunggren H-G, Löw P, Taraboulos A et al. Processing and degradation of exogenous prion protein by CD11c(+) myeloid dendritic cells in vitro. J Virol 2002; 76:12259–12264 [CrossRef][PubMed]
    [Google Scholar]
  58. Sethi S, Kerksiek KM, Brocker T, Kretzschmar H. Role of the CD8+ dendritic cell subset in transmission of prions. J Virol 2007; 81:4877–4880 [CrossRef][PubMed]
    [Google Scholar]
  59. Beekes M, McBride PA. The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies. Febs J 2007; 274:588–605 [CrossRef][PubMed]
    [Google Scholar]
  60. Mabbott NA, MacPherson GG. Prions and their lethal journey to the brain. Nat Rev Microbiol 2006; 4:201211 [CrossRef][PubMed]
    [Google Scholar]
  61. van Keulen LJM, Vromans MEW, van Zijderveld FG. Early and late pathogenesis of natural scrapie infection in sheep. APMIS 2002; 110:23–32 [CrossRef][PubMed]
    [Google Scholar]
  62. Heggebø R, Press CM, Gunnes G, González L, Jeffrey M. Distribution and accumulation of PrP in gut-associated and peripheral lymphoid tissue of scrapie-affected Suffolk sheep. J Gen Virol 2002; 83:479–489 [CrossRef][PubMed]
    [Google Scholar]
  63. Maignien T, Shakweh M, Calvo P, Marcé D, Salès N et al. Role of gut macrophages in mice orally contaminated with scrapie or BSE. Int J Pharm 2005; 298:293–304 [CrossRef][PubMed]
    [Google Scholar]
  64. Lacroux C, Vilette D, Fernández-Borges N, Litaise C, Lugan S et al. Prionemia and leukocyte-platelet-associated infectivity in sheep transmissible spongiform encephalopathy models. J Virol 2012; 86:2056–2066 [CrossRef][PubMed]
    [Google Scholar]
  65. McCutcheon S, Alejo Blanco AR, Houston EF, de Wolf C, Tan BC et al. All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD. PLoS One 2011; 6:e23169 [CrossRef][PubMed]
    [Google Scholar]
  66. Bons N, Lehmann S, Mestre-Francès N, Dormont D, Brown P. Brain and buffy coat transmission of bovine spongiform encephalopathy to the primate Microcebus murinus. Transfusion 2002; 42:513–516 [CrossRef][PubMed]
    [Google Scholar]
  67. Cassmann ED, Moore SJ, Smith JD, Greenlee JJ. Sheep with the homozygous Lysine-171 prion protein genotype are resistant to classical scrapie after experimental oronasal inoculation. Vet Pathol 2019; 56:409–417 [CrossRef][PubMed]
    [Google Scholar]
  68. Sisó S, Jeffrey M, Martin S, Chianini F, Dagleish MP et al. Characterization of strains of ovine transmissible spongiform encephalopathy with a short PrPd profiling method. J Comp Pathol 2010; 142:300–310 [CrossRef][PubMed]
    [Google Scholar]
  69. González L, Martin S, Begara-McGorum I, Hunter N, Houston F et al. Effects of agent strain and host genotype on PrP accumulation in the brain of sheep naturally and experimentally affected with scrapie. J Comp Pathol 2002; 126:17–29 [CrossRef][PubMed]
    [Google Scholar]
  70. González L, Pitarch JL, Martin S, Thurston L, Simmons H et al. Influence of polymorphisms in the prion protein gene on the pathogenesis and neuropathological phenotype of sheep scrapie after oral infection. J Comp Pathol 2014; 150:57–70 [CrossRef][PubMed]
    [Google Scholar]
  71. Ligios C, Jeffrey M, Ryder SJ, Bellworthy SJ, Simmons MM. Distinction of scrapie phenotypes in sheep by lesion profiling. J Comp Pathol 2002; 127:45–57 [CrossRef][PubMed]
    [Google Scholar]
  72. Begara-McGorum I, González L, Simmons M, Hunter N, Houston F et al. Vacuolar lesion profile in sheep scrapie: factors influencing its variation and relationship to disease-specific PrP accumulation. J Comp Pathol 2002; 127:59–68 [CrossRef][PubMed]
    [Google Scholar]
  73. Jeffrey M, González L. Classical sheep transmissible spongiform encephalopathies: pathogenesis, pathological phenotypes and clinical disease. Neuropathol Appl Neurobiol 2007; 33:373–394 [CrossRef][PubMed]
    [Google Scholar]
  74. Gregori L, McCombie N, Palmer D, Birch P, Sowemimo-Coker SO et al. Effectiveness of leucoreduction for removal of infectivity of transmissible spongiform encephalopathies from blood. The Lancet 2004; 364:529–531 [CrossRef]
    [Google Scholar]
  75. Prowse CV, Bailey A. Validation of prion removal by leucocyte-depleting filters: a cautionary tale. Vox Sang 2000; 79:248 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.0.000155
Loading
/content/journal/acmi/10.1099/acmi.0.000155
Loading

Data & Media loading...

Most cited this month 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