Prion potentiation after life-long dormancy in mice devoid of PrP

• DOI: 10.1093/braincomms/fcab092
• Publication Date: 2021-04-23T03:49:30Z
• Authors: Davy Martin; Fabienne Reine; Laetitia Herzog; Angélique Igel-Eg...; Naima Aron; Christel Michel; Mohammed Moudjou; Guillaume Fichet; Isabelle Quadrio; Armand Perret-Lia...; Olivier Andréoletti; Human Rezaei; Vincent Béringue
• Keywords: Infectivity

Abstract Prions are neurotropic pathogens composed of misfolded assemblies the host-encoded prion protein PrPC which replicate by recruitment and conversion further an autocatalytic seeding polymerization process. While it has long been shown that mouse-adapted prions cannot rapidly cleared in transgenic PrP0/0 mice invalidated for PrPC, these experiments have not done with other prions, including from natural resources, more sensitive methods to detect biological activity. Using expressing human PrP bioassay infectivity RT-QuIC cell-free assay measure activity, we report responsible most prevalent form sporadic Creutzfeldt–Jakob disease (MM1-sCJD) can persist indefinitely brain intra-cerebrally inoculated mice. low levels activity were measured challenged mice, bio-indicator humanized succumbed at a high attack rate, suggesting relatively persistent infectivity. Remarkably, delayed kinetics as compared MM1-sCJD directly doses, limiting one. Yet, did occur on primary subsequent back-passage shared neuropathological molecular characteristics no apparent strain evolution during lifelong dormancy brain. Thus, entire life potential potentiation retrotransmission susceptible hosts. These findings highlight capacity rejuvenate non-replicative environments, interrogate type work alert risk indefinite persistence PrP-lowering therapeutic strategies.