EMBO reports (2011) 12, 1243 - 1250
Published online: 14 October 2011
Mutability of prions EMBO Open
Jiali Li1, Sukhvir P Mahal1, Cheryl A Demczyk1 & Charles Weissmann1
Department of Infectology, Scripps Florida, 130 Scripps Way, Jupiter, Florida 33458, USA
Charles Weissmann, Tel: +1 561 228 3459; Fax: +1 561 228 3099;
Received 15 June 2011; Revised 6 September 2011; Accepted 8 September 2011
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 PrPScconformation. One clone remained swa incompetent even after 1035-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.
Keywords: mutation; selection; strain; substrain; swainsonine
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