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Stabilization of a prion strain of synthetic origin requires multiple serial passages


Makarava, Natallia; Kovacs, Gabor G; Savtchenko, Regina; Alexeeva, Irina; Budka, Herbert; Rohwer, Robert G; Baskakov, Ilia V (2012). Stabilization of a prion strain of synthetic origin requires multiple serial passages. Journal of Biological Chemistry, 287(36):30205-30214.

Abstract

Transmission of prions to a new host is frequently accompanied by strain adaptation, a phenomenon that involves reduction of the incubation period, a change in neuropathological features and, sometimes, tissue tropism. Here we show that a strain of synthetic origin (SSLOW), although serially transmitted within the same species, displayed the key attributes of the strain adaptation process. At least four serial passages were required to stabilize the strain-specific SSLOW phenotype. The biological titration of SSLOW revealed a correlation between clinical signs and accumulation of PrP(Sc) in brains of animals inoculated with high doses (10(-1)-10(-5) diluted brain material), but dissociation between the two processes at low dose inocula (10(-6)-10(-8) diluted brain material). At low doses, several asymptomatic animals harbored large amounts of PrP(Sc) comparable with those seen in the brains of terminally ill animals, whereas one clinically ill animal had very little, if any, PrP(Sc). In summary, the current study illustrates that the phenomenon of prion strain adaptation is more common than generally thought and could be observed upon serial transmission without changing the host species. When PrP(Sc) is seeded by recombinant PrP structures different from that of authentic PrP(Sc), PrP(Sc) properties continued to evolve for as long as four serial passages.

Abstract

Transmission of prions to a new host is frequently accompanied by strain adaptation, a phenomenon that involves reduction of the incubation period, a change in neuropathological features and, sometimes, tissue tropism. Here we show that a strain of synthetic origin (SSLOW), although serially transmitted within the same species, displayed the key attributes of the strain adaptation process. At least four serial passages were required to stabilize the strain-specific SSLOW phenotype. The biological titration of SSLOW revealed a correlation between clinical signs and accumulation of PrP(Sc) in brains of animals inoculated with high doses (10(-1)-10(-5) diluted brain material), but dissociation between the two processes at low dose inocula (10(-6)-10(-8) diluted brain material). At low doses, several asymptomatic animals harbored large amounts of PrP(Sc) comparable with those seen in the brains of terminally ill animals, whereas one clinically ill animal had very little, if any, PrP(Sc). In summary, the current study illustrates that the phenomenon of prion strain adaptation is more common than generally thought and could be observed upon serial transmission without changing the host species. When PrP(Sc) is seeded by recombinant PrP structures different from that of authentic PrP(Sc), PrP(Sc) properties continued to evolve for as long as four serial passages.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:21 Dec 2012 13:36
Last Modified:26 Aug 2016 07:32
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in: Makarava, Natallia; Kovacs, Gabor G; Savtchenko, Regina; Alexeeva, Irina; Budka, Herbert; Rohwer, Robert G; Baskakov, Ilia V (2012). Stabilization of a prion strain of synthetic origin requires multiple serial passages. Journal of Biological Chemistry, 287(36):30205-30214. © the American Society for Biochemistry and Molecular Biology
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1074/jbc.M112.392985
PubMed ID:22807452

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