title: Mutability of prions.
abstract: Murine prions transferred from brain to cultured cells gradually adapt to the new environment. Brain-derived 22L prions can infect neuroblastoma-derived PK1 cells in the presence of swainsonine (swa); that is, they are 'swa resistant'. PK1 cell-adapted 22L prions are swa sensitive; however, propagation in swa results in selection of swa-resistant substrains. Cloned, PK1 cell-adapted 22L prions were initially unable to develop swa resistance ('swa incompetent'); however, after serial propagation for 30-90 doublings, four of nine clones became swa competent, showing that swa-resistant 'mutants' arose during replication. Mutations in the case of prions are attributed to heritable changes in PrP(Sc) conformation. One clone remained swa incompetent even after 10(35)-fold expansion; surprisingly, after propagation in brain, it yielded swa-resistant prions, indistinguishable from the original 22L population. Thus, cell-adapted 22L prions assumed either mutable or virtually immutable conformations; however, when passaged through the brain all became mutable. Mutability is thus a substrain-specific attribute.
authors: Department of Infectology, Scripps Florida, 130 Scripps Way, Jupiter, Florida 33458, USA.
authors: Jiali
authors: J
authors: Li
authors: Sukhvir P
authors: SP
authors: Mahal
authors: Cheryl A
authors: CA
authors: Demczyk
authors: Charles
authors: C
authors: Weissmann
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002460:Cell Line; D002999:Clone Cells; D004351:Drug Resistance / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D011328:Prions / Q000235:genetics*; D017026:Swainsonine / Q000494:pharmacology; D014020:Tissue Extracts
chemical_list: D011328:Prions; D014020:Tissue Extracts; D017026:Swainsonine