Evolution of a strain of CJD that induces BSE-like plaques.
Bovine spongiform encephalopathy (BSE) has become a public health issue because a recently evolved BSE agent has infected people, yielding an unusual form of Creutzfeld-Jakob disease (CJD). A new CJD agent that provokes similar amyloid plaques and cerebellar pathology was serially propagated. First-passage rats showed obvious clinical signs and activated microglia but had negligible PrP-res (the more protease-resistant form of host PrP) or cerebellar lesions. Microglia and astrocytes may participate in strain selection because the agent evolved, stabilized, and reproducibly provoked BSE-like disease in subsequent passages. Early vacuolar change involving activated microglia and astrocytes preceded significant PrP-res accumulation by more than 50 days. These studies reveal several inflammatory host reactions to an exogenous agent.
Manuelidis
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L
Section of Neuropathology, Yale Medical School, 310 Cedar Street, New Haven, CT 06510, USA. laura.manuelidis@yale.edu
Fritch
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Xi
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D016564:Amyloid beta-Protein Precursor / Q000032:analysis; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000648:ultrastructure*; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D002531:Cerebellum / Q000737:chemistry / Q000473:pathology; D051152:Clusterin; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism / Q000473:pathology*; D006224:Cricetinae; D003412:Cricetulus; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000032:analysis; D007249:Inflammation; D008264:Macrophages / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000737:chemistry / Q000648:ultrastructure*; D008854:Microscopy, Electron; D018832:Molecular Chaperones; D018620:PrPSc Proteins / Q000032:analysis* / Q000472:pathogenicity; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014452:Ubiquitins / Q000032:analysis; D014617:Vacuoles / Q000648:ultrastructure; D014774:Virulence
D016564:Amyloid beta-Protein Precursor; C495243:Clu protein, mouse; D051152:Clusterin; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D018832:Molecular Chaperones; D018620:PrPSc Proteins; D014452:Ubiquitins; D012313:RNA