Genetic modulation of CWD prion propagation in cervid PrP Drosophila.

Autor:	Thackray AM; Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, U.K., McNulty EE; Prion Research Center (PRC) and the Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, U.S.A., Nalls AV; Prion Research Center (PRC) and the Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, U.S.A., Cardova A; Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, U.K., Tran L; Department of Biohazard and Pathology, WOAH Reference Laboratory for CWD (SLB), National Veterinary Institute, Postboks 64, 1431 Ås, Norway., Telling G; Prion Research Center (PRC) and the Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, U.S.A., Benestad SL; Department of Biohazard and Pathology, WOAH Reference Laboratory for CWD (SLB), National Veterinary Institute, Postboks 64, 1431 Ås, Norway., Gilch S; Faculty of Veterinary Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada., Mathiason CK; Prion Research Center (PRC) and the Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, U.S.A., Bujdoso R; Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, U.K.
Jazyk:	angličtina
Zdroj:	The Biochemical journal [Biochem J] 2023 Oct 11; Vol. 480 (19), pp. 1485-1501.
DOI:	10.1042/BCJ20230247
Abstrakt:	Chronic wasting disease is a fatal prion condition of cervids such as deer, elk, moose and reindeer. Secretion and excretion of prion infectivity from North American cervids with this condition causes environmental contamination and subsequent efficient lateral transmission in free-ranging and farmed cervids. Variants of cervid PrP exist that affect host susceptibility to chronic wasting disease. Cervid breeding programmes aimed at increasing the frequency of PrP variants associated with resistance to chronic wasting disease may reduce the burden of this condition in animals and lower the risk of zoonotic disease. This strategy requires a relatively rapid and economically viable model system to characterise and support selection of prion disease-modifying cervid PrP variants. Here, we generated cervid PrP transgenic Drosophila to fulfil this purpose. We have generated Drosophila transgenic for S138 wild type cervid PrP, or the N138 variant associated with resistance to chronic wasting disease. We show that cervid PrP Drosophila accumulate bona fide prion infectivity after exposure to cervid prions. Furthermore, S138 and N138 PrP fly lines are susceptible to cervid prion isolates from either North America or Europe when assessed phenotypically by accelerated loss of locomotor ability or survival, or biochemically by accumulation of prion seeding activity. However, after exposure to European reindeer prions, N138 PrP Drosophila accumulated prion seeding activity with slower kinetics than the S138 fly line. These novel data show that prion susceptibility characteristics of cervid PrP variants are maintained when expressed in Drosophila, which highlights this novel invertebrate host in modelling chronic wasting disease. (© 2023 The Author(s).)
Databáze:	MEDLINE
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