411: EKV cells and the Human Prion Assay: a scalable platform for sCJD infectivity

Nihata A et al., PNAS - This PNAS study describes the development of EKV, a humanized dividing cell line that propagates bona fide sporadic CJD (sCJD) prions, and the Human Prion Assay (HPA), a cell-based method that quantifies infectivity with sensitivity comparable to transgenic mouse bioassay while enabling rapid therapeutic screening. Key terms: sCJD, EKV cells, Human Prion Assay, prion infectivity, anti-PrP antibody. Study Highlights:The authors engineered EKV cells by reconstituting CAD5 PrP-knockdown cells with human PrP (V129) and iterative single-cell cloning to enrich prion susceptibility. EKV cells propagate de novo infectious sCJD prions that reproduce strain-specific pathology when transmitted to humanized Tg152c mice. The Human Prion Assay (HPA) using EKV cells quantifies sCJD infectivity across a wide dynamic range with sensitivity comparable to mouse bioassay but in weeks rather than years. Persistently infected iEKV clones can be cured by the anti-PrP monoclonal antibody ICSM18, validating the platform for high-throughput therapeutic screens. Conclusion:EKV cells and the HPA provide a renewable, scalable, and faster alternative to animal bioassays for measuring authentic human sCJD infectivity and for screening and validating anti-prion therapeutics, while retaining strain-specific biological properties. Music:Enjoy the music based on this article at the end of the episode. Article title:A scalable, dividing cell model for the robust propagation and quantification of human sporadic Creutzfeldt–Jakob disease prions First author:Nihata A Journal:PNAS DOI:10.1073/pnas.2600341123 Reference:Nihata A, Collinge J, Linehan J, Brandner S, Mead S, Schmidt C, Rayner MLD, Jat PS, Arora P, et al. A scalable, dividing cell model for the robust propagation and quantification of human sporadic Creutzfeldt–Jakob disease prions. PNAS. 2026;123(27):e2600341123. doi:10.1073/pnas.2600341123. License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming:❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at basebybase.com On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/ekv-human-prion-assay QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-09. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Substantive audit focused on EKV cell development and validation, in vitro propagation of human sCJD prions, HPA implementation and benchmarking against mouse bioassay, drug-screening demonstration, and documented limitations (codon 129 mismatch, occult infectivity).- transcript topics: Prion biology and strain concepts (PRNP codon 129 polymorphism); Historical barriers to human prion culture and need for cell-based infectivity assays; Engineering EKV cells: CAD5-KDB3, human PrP V129, mouse signal peptide; Iterative single-cell cloning and enrichment to EKV; Infectivity validation via transmission to Tg152c mice; Development and validation of the Human Prion Assay (HPA) QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 6- claims flagged for review: 0- metadata checks passed: 4-...