Norwegian moose CWD induces clinical disease and neuroinvasion in gene-targeted mice expressing cervid S138N prion protein.

Autor: Arifin MI; Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada., Hannaoui S; Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada., Ng RA; Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada., Zeng D; Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada., Zemlyankina I; Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada., Ahmed-Hassan H; Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada.; Zoonoses Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt., Schatzl HM; Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Canada., Kaczmarczyk L; Linköping University, Linköping, Sweden., Jackson WS; Linköping University, Linköping, Sweden., Benestad SL; Norwegian Veterinary Institute, Ås, Norway., Gilch S; Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.; Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Canada.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Jul 01; Vol. 20 (7), pp. e1012350. Date of Electronic Publication: 2024 Jul 01 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012350
Abstrakt: Chronic wasting disease (CWD) is a prion disease affecting deer, elk and moose in North America and reindeer, moose and red deer in Northern Europe. Pathogenesis is driven by the accumulation of PrPSc, a pathological form of the host's cellular prion protein (PrPC), in the brain. CWD is contagious among North American cervids and Norwegian reindeer, with prions commonly found in lymphatic tissue. In Nordic moose and red deer CWD appears exclusively in older animals, and prions are confined to the CNS and undetectable in lymphatic tissues, indicating a sporadic origin. We aimed to determine transmissibility, neuroinvasion and lymphotropism of Nordic CWD isolates using gene-targeted mice expressing either wild-type (138SS/226QQ) or S138N (138NN/226QQ) deer PrP. When challenged with North American CWD strains, mice expressing S138N PrP did not develop clinical disease but harbored prion seeding activity in brain and spleen. Here, we infected these models intracerebrally or intraperitoneally with Norwegian moose, red deer and reindeer CWD isolates. The moose isolate was the first CWD type to cause full-blown disease in the 138NN/226QQ model in the first passage, with 100% attack rate and shortened survival times upon second passage. Furthermore, we detected prion seeding activity or PrPSc in brains and spinal cords, but not spleens, of 138NN/226QQ mice inoculated intraperitoneally with the moose isolate, providing evidence of prion neuroinvasion. We also demonstrate, for the first time, that transmissibility of the red deer CWD isolate was restricted to transgenic mice overexpressing elk PrPC (138SS/226EE), identical to the PrP primary structure of the inoculum. Our findings highlight that susceptibility to clinical disease is determined by the conformational compatibility between prion inoculum and host PrP primary structure. Our study indicates that neuroinvasion of Norwegian moose prions can occur without, or only very limited, replication in the spleen, an unprecedented finding for CWD.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Arifin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje