Volume 31, Number 12—December 2025
Dispatch
Abnormal Prion Protein in Nasal Swab Specimens of Macaques Infected with Creutzfeldt-Jakob Disease
Table 2
Summary of test results from study of abnormal prion protein in nasal swab specimens of macaques infected with Creutzfeldt-Jakob disease*
| Recipient macaque ID | Clinical status | Tissue tested | Western blot† | RT-QuIC | PMCA | Histology | Total mice inoculated/ positive results‡ |
|---|---|---|---|---|---|---|---|
| CO1619 | Asymptomatic | Brain | Neg | Neg | Neg | Neg | 40/0 |
| Spleen | ND | ND | Neg | ND | 10/0 | ||
| Ileum | ND | ND | Neg | ND | 15/0 | ||
| Blood | NA | NA | Neg | N/A | ND | ||
| Nasal swab | ND | Neg | Neg | NA | ND | ||
| 98CO19 | Asymptomatic | Brain | Neg | Neg | Neg | Neg | 51/0 |
| Blood | NA | ND | Neg | NA | ND | ||
| Nasal swab | ND | W pos | Neg | NA | ND | ||
| Lymph node | ND | W pos | Neg | Pos | ND | ||
| DEIM | Symptomatic | Brain | Pos | ND | ND | Pos | ND |
| Blood | NA | NA | Pos | NA | ND | ||
| Nasal swabs | ND | Pos | Pos | NA | ND | ||
| CSF | ND | Pos | ND | NA | ND | ||
| DFOO | Asymptomatic | Brain | Neg | Neg | Neg | Neg | ND |
| Blood | NA | NA | Neg | NA | ND | ||
| Nasal swab | ND | Neg | Neg | NA | ND | ||
| CSF | Neg | Neg | Neg | NA | ND |
*CSF, cerebrospinal fluid; pos, TSE positive; W pos, weak TSE positive; neg, TSE negative; NA, not applicable; ND, not done; RT-QuIC, real-time quaking-induced conversion; TSE, transmissible spongiform encephalopathy. †We used 10% homogenates in phosphate-buffered saline, treated with 20 U/mL of benzonase nuclease for 30 minutes at room temperature with constant mixing, followed with 50 μg/mL proteinase K for 1 hour at 37°C to remove normal prion protein. Samples were processed for NuPAGE on 12% Bis-Tris precast gels (Thermo Fisher Scientific, https://www.thermofisher.com), prion protein detected using 3F4 mouse anti-PrP monoclonal antibody (Research Foundation for Mental Hygiene, New York State Institute for Basic Research; https://corporate.rfmh.org/). ‡We inoculated intracerebrally 30-µL aliquots of 1% tissue homogenates into transgenic mice overexpressing the bovine prion protein, TgBo110 (10). We monitored mice for 2 years for signs of vCJD and tested the brain of every mouse for PrPTSE with real-time quaking-induced conversion.
References
- Will R. Variant Creutzfeldt-Jakob disease. Folia Neuropathol. 2004;42 Suppl A:77-83.
- Ironside JW. Variant Creutzfeldt-Jakob disease: an update. Folia Neuropathol. 2012;50:50–6.PubMedGoogle Scholar
- Belay ED, Schonberger LB. Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. [v–vi.]. Clin Lab Med. 2002;22:849–62, v–vi.PubMedGoogle Scholar
- Turner ML, Ludlam CA. An update on the assessment and management of the risk of transmission of variant Creutzfeldt-Jakob disease by blood and plasma products. Br J Haematol. 2009;144:14–23.PubMedGoogle Scholar
- Seed CR, Hewitt PE, Dodd RY, Houston F, Cervenakova L. Creutzfeldt-Jakob disease and blood transfusion safety. Vox Sang. 2018;113:220–31.PubMedGoogle Scholar
- Yakovleva O, Bett C, Pilant T, Asher DM, Gregori L. Abnormal prion protein, infectivity and neurofilament light-chain in blood of macaques with experimental variant Creutzfeldt-Jakob disease. J Gen Virol. 2022;103:
001764 .PubMedGoogle Scholar - McDowell KL, Nag N, Franco Z, Bu M, Piccardo P, Cervenak J, et al. Blood reference materials from macaques infected with variant Creutzfeldt-Jakob disease agent. Transfusion. 2015;55:405–12.PubMedGoogle Scholar
- Atarashi R, Moore RA, Sim VL, Hughson AG, Dorward DW, Onwubiko HA, et al. Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein. Nat Methods. 2007;4:645–50.PubMedGoogle Scholar
- Chen B, Morales R, Barria MA, Soto C. Estimating prion concentration in fluids and tissues by quantitative PMCA. Nat Methods. 2010;7:519–20.PubMedGoogle Scholar
- Castilla J, Gutiérrez Adán A, Brun A, Pintado B, Ramírez MA, Parra B, et al. Early detection of PrPres in BSE-infected bovine PrP transgenic mice. Arch Virol. 2003;148:677–91.PubMedGoogle Scholar
- Lescoutra-Etchegaray N, Jaffré N, Sumian C, Durand V, Correia E, Mikol J, et al. Evaluation of the protection of primates transfused with variant Creutzfeldt-Jakob disease-infected blood products filtered with prion removal devices: a 5-year update. Transfusion. 2015;55:1231–41.PubMedGoogle Scholar
- Comoy EE, Mikol J, Jaffré N, Lebon V, Levavasseur E, Streichenberger N, et al. Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque. Nat Commun. 2017;8:1268.PubMedGoogle Scholar
- Gregori L, Yang H, Anderson S. Estimation of variant Creutzfeldt-Jakob disease infectivity titers in human blood. Transfusion. 2011;51:2596–602.PubMedGoogle Scholar
- Fiorini M, Iselle G, Perra D, Bongianni M, Capaldi S, Sacchetto L, et al. High diagnostic accuracy of RT-QuIC assay in a prospective study of patients with suspected sCJD. Int J Mol Sci. 2020;21:880.PubMedGoogle Scholar
- Vallabh SM, Minikel EV, Schreiber SL, Lander ES. Towards a treatment for genetic prion disease: trials and biomarkers. Lancet Neurol. 2020;19:361–8.PubMedGoogle Scholar
1Retired.