Highly Efficient Prion Transmission by Blood Transfusion
It is now clearly established that the transfusion of blood from variant CJD (v-CJD) infected individuals can transmit the disease. Since the number of asymptomatic infected donors remains unresolved, inter-individual v-CJD transmission through blood and blood derived products is a major public health concern. Current risk assessments for transmission of v-CJD by blood and blood derived products by transfusion rely on infectious titers measured in rodent models of Transmissible Spongiform Encephalopathies (TSE) using intra-cerebral (IC) inoculation of blood components. To address the biological relevance of this approach, we compared the efficiency of TSE transmission by blood and blood components when administrated either through transfusion in sheep or by intra-cerebral inoculation (IC) in transgenic mice (tg338) over-expressing ovine PrP. Transfusion of 200 µL of blood from asymptomatic infected donor sheep transmitted prion disease with 100% efficiency thereby displaying greater virulence than the transfusion of 200 mL of normal blood spiked with brain homogenate material containing 103ID50 as measured by intracerebral inoculation of tg338 mice (ID50 IC in tg338). This was consistent with a whole blood titer greater than 103.6 ID50 IC in tg338 per mL. However, when the same blood samples were assayed by IC inoculation into tg338 the infectious titers were less than 32 ID per mL. Whereas the transfusion of crude plasma to sheep transmitted the disease with limited efficacy, White Blood Cells (WBC) displayed a similar ability to whole blood to infect recipients. Strikingly, fixation of WBC with paraformaldehyde did not affect the infectivity titer as measured in tg338 but dramatically impaired disease transmission by transfusion in sheep. These results demonstrate that TSE transmission by blood transfusion can be highly efficient and that this efficiency is more dependent on the viability of transfused cells than the level of infectivity measured by IC inoculation.
Vyšlo v časopise:
Highly Efficient Prion Transmission by Blood Transfusion. PLoS Pathog 8(6): e32767. doi:10.1371/journal.ppat.1002782
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002782
Souhrn
It is now clearly established that the transfusion of blood from variant CJD (v-CJD) infected individuals can transmit the disease. Since the number of asymptomatic infected donors remains unresolved, inter-individual v-CJD transmission through blood and blood derived products is a major public health concern. Current risk assessments for transmission of v-CJD by blood and blood derived products by transfusion rely on infectious titers measured in rodent models of Transmissible Spongiform Encephalopathies (TSE) using intra-cerebral (IC) inoculation of blood components. To address the biological relevance of this approach, we compared the efficiency of TSE transmission by blood and blood components when administrated either through transfusion in sheep or by intra-cerebral inoculation (IC) in transgenic mice (tg338) over-expressing ovine PrP. Transfusion of 200 µL of blood from asymptomatic infected donor sheep transmitted prion disease with 100% efficiency thereby displaying greater virulence than the transfusion of 200 mL of normal blood spiked with brain homogenate material containing 103ID50 as measured by intracerebral inoculation of tg338 mice (ID50 IC in tg338). This was consistent with a whole blood titer greater than 103.6 ID50 IC in tg338 per mL. However, when the same blood samples were assayed by IC inoculation into tg338 the infectious titers were less than 32 ID per mL. Whereas the transfusion of crude plasma to sheep transmitted the disease with limited efficacy, White Blood Cells (WBC) displayed a similar ability to whole blood to infect recipients. Strikingly, fixation of WBC with paraformaldehyde did not affect the infectivity titer as measured in tg338 but dramatically impaired disease transmission by transfusion in sheep. These results demonstrate that TSE transmission by blood transfusion can be highly efficient and that this efficiency is more dependent on the viability of transfused cells than the level of infectivity measured by IC inoculation.
Zdroje
1. BruceMEWillRGIronsideJWMcConnellIDrummondD 1997 Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389 498 501
2. CollingeJSidleKCMeadsJIronsideJHillAF 1996 Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383 685 690
3. LlewelynCAHewittPEKnightRSAmarKCousensS 2004 Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 363 417 421
4. LefrereJJHewittP 2009 From mad cows to sensible blood transfusion: the risk of prion transmission by labile blood components in the United Kingdom and in France. Transfusion 49 797 812
5. GregoriLMcCombieNPalmerDBirchPSowemimo-CokerSO 2004 Effectiveness of leucoreduction for removal of infectivity of transmissible spongiform encephalopathies from blood. Lancet 364 529 531
6. BrownPRohwerRGDunstanBCMacAuleyCGajdusekDC 1998 The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy. Transfusion 38 810 816
7. BrownPCervenakovaLMcShaneLMBarberPRubensteinR 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
8. CervenakovaLYakovlevaOMcKenzieCKolchinskySMcShaneL 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
9. HoladaKVostalJGTheisenPWMacAuleyCGregoriL 2002 Scrapie infectivity in hamster blood is not associated with platelets. J Virol 76 4649 4650
10. GregoriLGurgelPVLathropJTEdwardsonPLambertBC 2006 Reduction in infectivity of endogenous transmissible spongiform encephalopathies present in blood by adsorption to selective affinity resins. Lancet 368 2226 2230
11. HoustonFFosterJDChongAHunterNBostockCJ 2000 Transmission of BSE by blood transfusion in sheep. Lancet 356 999 1000
12. HunterNFosterJChongAMcCutcheonSParnhamD 2002 Transmission of prion diseases by blood transfusion. J Gen Virol 83 2897 2905
13. IronsideJWBishopMTConnollyKHegazyDLowrieS 2006 Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive appendix tissue samples from a retrospective prevalence study. BMJ 332 1186 1188
14. IronsideJWHiltonDAGhaniAJohnstonNJConyersL 2000 Retrospective study of prion-protein accumulation in tonsil and appendix tissues. Lancet 355 1693 1694
15. SimmonsHASimmonsMMSpencerYIChaplinMJPoveyG 2009 Atypical scrapie in sheep from a UK research flock which is free from classical scrapie. BMC Vet Res 5 8
16. AndreolettiOOrgeLBenestadSLBeringueVLitaiseC 2011 Atypical/Nor98 scrapie infectivity in sheep peripheral tissues. PLoS Pathog 7 e1001285
17. ArsacJNAndreolettiOBilheudeJMLacrouxCBenestadSL 2007 Similar biochemical signatures and prion protein genotypes in atypical scrapie and Nor98 cases, France and Norway. Emerg Infect Dis 13 58 65
18. Le DurABeringueVAndreolettiOReineFLaiTL 2005 A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes. Proc Natl Acad Sci U S A 102 16031 16036
19. MarkusRAFrankJGroshenSAzenSP 1995 An alternative approach to the optimal design of an LD50 bioassay. Stat Med 14 841 852
20. FisherRA 1936 Uncertain Inference. P Am Acad Arts Sci 71 245 258
21. GregoriLLambertBCGurgelPVGheorghiuLEdwardsonP 2006 Reduction of transmissible spongiform encephalopathy infectivity from human red blood cells with prion protein affinity ligands. Transfusion 46 1152 1161
22. LacrouxCCorbiereFTabouretGLuganSCostesP 2007 Dynamics and genetics of PrPSc placental accumulation in sheep. J Gen Virol 88 1056 1061
23. BrownPCervenakovaLMcShaneLMBarberPRubensteinR 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
24. BrownPLiberskiPPWolffAGajdusekDC 1990 Resistance of scrapie infectivity to steam autoclaving after formaldehyde fixation and limited survival after ashing at 360 degrees C: practical and theoretical implications. J Infect Dis 161 467 472
25. WadsworthJDDalmau-MenaIJoinerSLinehanJMO'MalleyC 2010 Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study. J Pathol 223 511 8
26. BrownPRohwerRGGreenEMGajdusekDC 1982 Effect of chemicals, heat, and histopathologic processing on high-infectivity hamster-adapted scrapie virus. J Infect Dis 145 683 687
27. KawakamiKKakimotoKShinboriTOnoueK 1989 Signal delivery by physical interaction and soluble factors from accessory cells in the induction of receptor-mediated T-cell proliferation. Synergistic effect of BSF-2/IL-6 and IL-1. Immunology 67 314 320
28. Peguet-NavarroJDalbiez-GauthierCSchmittD 1992 Accessory function of human Langerhans cells in the primary allogeneic T-cell response. J Invest Dermatol 99 87S 88S
29. KanuNImokawaYDrechselDNWilliamsonRABirkettCR 2002 Transfer of scrapie prion infectivity by cell contact in culture. Curr Biol 12 523 530
30. PaquetSLangevinCChapuisJJacksonGSLaudeH 2007 Efficient dissemination of prions through preferential transmission to nearby cells. J Gen Virol 88 706 713
31. AucouturierPGeissmannFDamotteDSaborioGPMeekerHC 2001 Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie. J Clin Invest 108 703 708
32. McCutcheonSAlejo BlancoARHoustonEFde WolfCTanBC 2011 All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD. PLoS One 6 e23169
33. MathiasonCKHayes-KlugJHaysSAPowersJOsbornDA 2010 B cells and platelets harbor prion infectivity in the blood of deer infected with chronic wasting disease. J Virol 84 5097 5107
34. VamvakasEC 2011 Universal white blood cell reduction in Europe: has transmission of variant Creutzfeldt-Jakob disease been prevented? Transfus Med Rev 25 133 144
35. MoralesRBuytaert-HoefenKAGonzalez-RomeroDCastillaJHansenET 2008 Reduction of prion infectivity in packed red blood cells. Biochem Biophys Res Commun 377 373 378
36. CardoneFSimoneauSArzelAPuopoloMBerardiVA 2012 Comparison of nanofiltration efficacy in reducing infectivity of centrifuged versus ultracentrifuged 263 K scrapie-infected brain homogenates in “spiked” albumin solutions. Transfusion 52 953 962
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2012 Číslo 6
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Manipulation of Costimulatory Molecules by Intracellular Pathogens: Veni, Vidi, Vici!!
- A Highly Intensified ART Regimen Induces Long-Term Viral Suppression and Restriction of the Viral Reservoir in a Simian AIDS Model
- An Endogenous Foamy-like Viral Element in the Coelacanth Genome
- The Interdomain Linker of AAV-2 Rep68 Is an Integral Part of Its Oligomerization Domain: Role of a Conserved SF3 Helicase Residue in Oligomerization