Table - Lack of Transmission of Chronic Wasting Disease Prions to Human Cerebral Organoids - Volume 30, Number 6—June 2024 - Emerging Infectious Diseases journal (2024)

Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.

Bradley R. Groveman1, Katie Williams1, Brent Race, Simote Foliaki, Tina Thomas, Andrew G. Hughson, Ryan O. Walters, Wenquan Zou, and Cathryn L. Haigh

Author affiliations: Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA (B.R. Groveman, K. Williams, B. Race, S. Foliaki, T. Tomas, A.G. Hughson, R.O. Walters, C.L. Haigh); Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, China (W. Zou)

Inoculum details used in the study of attempted CWD prion transmission to human cerebral organoids*

SampleNamelog LD50/mg brain†log SD50/mg brain‡
Human normal brain hom*ogenatehNBHNegativeNegative
Human sporadic CJD MV2CJDND6.9
Deer normal brain hom*ogenatedNBHNegativeNegative
White tail deer CWD§ (pool of 7)dCWD15.6 (WTD)6
Mule deer CWD¶ (pool of 6)dCWD25.7 (MD)6.2
Elk normal brain hom*ogenateeNBHNegativeNegative
Elk CWD# (pool of 6)eCWD5.36.5

*CJD, Creutzfeldt-Jakob disease; CWD, chronic wasting disease; LD50, 50% lethal dose; negative,negative control; ND,not done; SD50, 50% seeding dose.†Adapted from Foliaki et al. (26). ‡Inocula. §WTD-1 in nomenclature as found in (29).¶MD-1 in nomenclature as found in (29)#Elk-2 in nomenclature as found in (29).

  1. Benestad SL, Telling GC. Chronic wasting disease: an evolving prion disease of cervids. Handb Clin Neurol. 2018;153:13551. DOIPubMedGoogle Scholar

  2. Kraus A, Groveman BR, Caughey B. Prions and the potential transmissibility of protein misfolding diseases. Annu Rev Microbiol. 2013;67:54364. DOIPubMedGoogle Scholar

  3. Igel A, Fornara B, Rezaei H, Béringue V. Prion assemblies: structural heterogeneity, mechanisms of formation, and role in species barrier. Cell Tissue Res. 2023;392:14966. DOIPubMedGoogle Scholar

  4. Lewis PA, Tattum MH, Jones S, Bhelt D, Batchelor M, Clarke AR, et al. Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formation. J Gen Virol. 2006;87:24439. DOIPubMedGoogle Scholar

  5. Bishop M. Influence of the prion protein gene codon 129 genotype on the clinical and pathological phenotype of human prion disease, and transmission to transgenic mice. In: Collins SJ, Lawson VA, editors. The cellular and molecular biology of prion disease. Kerala (India): Research Signpost; 2011. p. 173–188.

  6. Kaski D, Mead S, Hyare H, Cooper S, Jampana R, Overell J, et al. Variant CJD in an individual heterozygous for PRNP codon 129. Lancet. 2009;374:2128. DOIPubMedGoogle Scholar

  7. Mok T, Jaunmuktane Z, Joiner S, Campbell T, Morgan C, Wakerley B, et al. Variant Creutzfeldt-Jakob disease in a patient with heterozygosity at PRNP codon 129. N Engl J Med. 2017;376:2924. DOIPubMedGoogle Scholar

  8. Smith PG, Cousens SN, d’ Huillard Aignaux JN, Ward HJT, Will RG. The epidemiology of variant Creutzfeldt-Jakob disease. Curr Top Microbiol Immunol. 2004;284:16191. DOIPubMedGoogle Scholar

  9. Gill ON, Spencer Y, Richard-Loendt A, Kelly C, Dabaghian R, Boyes L, et al. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ. 2013;347(oct15 5):f5675.

  10. Gill ON, Spencer Y, Richard-Loendt A, Kelly C, Brown D, Sinka K, et al. Prevalence in Britain of abnormal prion protein in human appendices before and after exposure to the cattle BSE epizootic. Acta Neuropathol. 2020;139:96576. DOIPubMedGoogle Scholar

  11. Barria MA, Libori A, Mitchell G, Head MW. Susceptibility of human prion protein to conversion by chronic wasting disease prions. Emerg Infect Dis. 2018;24:14829. DOIPubMedGoogle Scholar

  12. Raymond GJ, Bossers A, Raymond LD, O’Rourke KI, McHolland LE, Bryant PK III, et al. Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO J. 2000;19:442530. DOIPubMedGoogle Scholar

  13. Kong Q, Huang S, Zou W, Vanegas D, Wang M, Wu D, et al. Chronic wasting disease of elk: transmissibility to humans examined by transgenic mouse models. J Neurosci. 2005;25:79449. DOIPubMedGoogle Scholar

  14. Sandberg MK, Al-Doujaily H, Sigurdson CJ, Glatzel M, O’Malley C, Powell C, et al. Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein. J Gen Virol. 2010;91:26517. DOIPubMedGoogle Scholar

  15. Tamgüney G, Giles K, Bouzamondo-Bernstein E, Bosque PJ, Miller MW, Safar J, et al. Transmission of elk and deer prions to transgenic mice. J Virol. 2006;80:910414. DOIPubMedGoogle Scholar

  16. Wilson R, Plinston C, Hunter N, Casalone C, Corona C, Tagliavini F, et al. Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein. J Gen Virol. 2012;93:16249. DOIPubMedGoogle Scholar

  17. Wadsworth JDF, Joiner S, Linehan JM, Jack K, Al-Doujaily H, Costa H, et al. Humanized transgenic mice are resistant to chronic wasting disease prions from Norwegian reindeer and moose. J Infect Dis. 2022;226:9337. DOIPubMedGoogle Scholar

  18. Race B, Williams K, Chesebro B. Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assay. Vet Res (Faisalabad). 2019;50:6. DOIPubMedGoogle Scholar

  19. Race B, Baune C, Williams K, Striebel JF, Hughson AG, Chesebro B. Second passage experiments of chronic wasting disease in transgenic mice overexpressing human prion protein. Vet Res (Faisalabad). 2022;53:111. DOIPubMedGoogle Scholar

  20. Hannaoui S, Zemlyankina I, Chang SC, Arifin MI, Béringue V, McKenzie D, et al. Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD. Acta Neuropathol. 2022;144:76784. DOIPubMedGoogle Scholar

  21. Race B, Meade-White KD, Phillips K, Striebel J, Race R, Chesebro B. Chronic wasting disease agents in nonhuman primates. Emerg Infect Dis. 2014;20:8337. DOIPubMedGoogle Scholar

  22. Race B, Williams K, Orrú CD, Hughson AG, Lubke L, Chesebro B. Lack of transmission of chronic wasting disease to cynomolgus macaques. J Virol. 2018;92:e0055018. DOIPubMedGoogle Scholar

  23. Lasmézas CI, Deslys J-P, Demaimay R, Adjou KT, Lamoury F, Dormont D, et al. BSE transmission to macaques. Nature. 1996;381:7434. DOIPubMedGoogle Scholar

  24. Groveman BR, Ferreira NC, Foliaki ST, Walters RO, Winkler CW, Race B, et al. Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt-Jakob disease. Sci Rep. 2021;11:5165. DOIPubMedGoogle Scholar

  25. Groveman BR, Foliaki ST, Orru CD, Zanusso G, Carroll JA, Race B, et al. Sporadic Creutzfeldt-Jakob disease prion infection of human cerebral organoids. Acta Neuropathol Commun. 2019;7:90. DOIPubMedGoogle Scholar

  26. Foliaki ST, Schwarz B, Groveman BR, Walters RO, Ferreira NC, Orrù CD, et al. Neuronal excitatory-to-inhibitory balance is altered in cerebral organoid models of genetic neurological diseases. Mol Brain. 2021;14:156. DOIPubMedGoogle Scholar

  27. Lancaster MA, Knoblich JA. Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc. 2014;9:232940. DOIPubMedGoogle Scholar

  28. Renner M, Lancaster MA, Bian S, Choi H, Ku T, Peer A, et al. Self-organized developmental patterning and differentiation in cerebral organoids. EMBO J. 2017;36:131629. DOIPubMedGoogle Scholar

  29. Race B, Meade-White KD, Miller MW, Barbian KD, Rubenstein R, LaFauci G, et al. Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis. 2009;15:136676. DOIPubMedGoogle Scholar

  30. Féraudet C, Morel N, Simon S, Volland H, Frobert Y, Créminon C, et al. Screening of 145 anti-PrP monoclonal antibodies for their capacity to inhibit PrPSc replication in infected cells. J Biol Chem. 2005;280:1124758. DOIPubMedGoogle Scholar

  31. O’Rourke KI, Baszler TV, Besser TE, Miller JM, Cutlip RC, Wells GAH, et al. Preclinical diagnosis of scrapie by immunohistochemistry of third eyelid lymphoid tissue. J Clin Microbiol. 2000;38:32549. DOIPubMedGoogle Scholar

  32. Groveman BR, Race B, Foliaki ST, Williams K, Hughson AG, Baune C, et al. Sporadic Creutzfeldt-Jakob disease infected human cerebral organoids retain the original human brain subtype features following transmission to humanized transgenic mice. Acta Neuropathol Commun. 2023;11:28. DOIPubMedGoogle Scholar

  33. Smith A, Groveman BR, Winkler C, Williams K, Walters R, Yuan J, et al. Stress and viral insults do not trigger E200K PrP conversion in human cerebral organoids. PLoS One. 2022;17:


    . DOIPubMedGoogle Scholar

  34. Wang Z, Qin K, Camacho MV, Cali I, Yuan J, Shen P, et al. Generation of human chronic wasting disease in transgenic mice. Acta Neuropathol Commun. 2021;9:158. DOIPubMedGoogle Scholar

  35. Haigh CL, Drew SC. Cavitation during the protein misfolding cyclic amplification (PMCA) method—The trigger for de novo prion generation? Biochem Biophys Res Commun. 2015;461:494500. DOIPubMedGoogle Scholar

  36. Lasmézas CI, Deslys J-P, Demaimay R, Adjou KT, Lamoury F, Dormont D, et al. BSE transmission to macaques. Nature. 1996;381:7434. DOIPubMedGoogle Scholar

  37. Montag J, Schulz-Schaeffer W, Schrod A, Hunsmann G, Motzkus D. Asynchronous onset of clinical disease in BSE-infected macaques. Emerg Infect Dis. 2013;19:11257. DOIPubMedGoogle Scholar

  38. Espinosa JC, Comoy EE, Marin-Moreno A, Aguilar-Calvo P, Birling M-C, Pitarch JL, et al. Transgenic mouse models expressing human and macaque prion protein exhibit similar prion susceptibility on a strain-dependent manner. Sci Rep. 2019;9:15699. DOIPubMedGoogle Scholar

  39. Asante EA, Linehan JM, Desbruslais M, Joiner S, Gowland I, Wood AL, et al. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J. 2002;21:635866. DOIPubMedGoogle Scholar

  40. Walters RO, Haigh CL. Organoids for modeling prion diseases. Cell Tissue Res. 2023;392:97111. DOIPubMedGoogle Scholar

1These authors contributed equally to this article.

The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsem*nt by any of the groups named above.

Table - Lack of Transmission of Chronic Wasting Disease Prions to Human Cerebral Organoids - Volume 30, Number 6—June 2024 - Emerging Infectious Diseases journal (2024)
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