Studies in bank voles reveal strain differences between chronic wasting disease prions from Norway and North America

Romolo Nonno; Michele A. Di Bari; Laura Pirisinu; Claudia D’Agostino; Ilaria Vanni; Barbara Chiappini; Stefano Marcon; Geraldina Riccardi; Linh Tran; Turid Vikøren; Jørn Våge; Knut Madslien; Gordon Mitchell; Glenn C. Telling; Sylvie L. Benestad; Umberto Agrimi

doi:10.1073/pnas.2013237117

New Research In

Edited by Michael B. A. Oldstone, Scripps Research Institute, La Jolla, CA, and approved November 3, 2020 (received for review June 26, 2020)

Significance

Chronic wasting disease (CWD) is a highly contagious disease caused by prions that affects several cervid species and is relentlessly spreading across North America. Very recently, CWD was detected for the first time in Europe. In this study, we found that Norwegian CWD strains are distinct from those causing the epidemic in North America. Moreover, we show that Norwegian reindeer and moose are affected by different CWD strains, revealing an unprecedented prion strain variation in Norwegian wild cervid populations. These findings indicate that North American CWD prions are not the proximate cause of the newly discovered Norwegian CWD cases and have implications for CWD control strategies in Europe, as well as for the safety of humans.

Abstract

Chronic wasting disease (CWD) is a relentless epidemic disorder caused by infectious prions that threatens the survival of cervid populations and raises increasing public health concerns in North America. In Europe, CWD was detected for the first time in wild Norwegian reindeer (Rangifer tarandus) and moose (Alces alces) in 2016. In this study, we aimed at comparing the strain properties of CWD prions derived from different cervid species in Norway and North America. Using a classical strain typing approach involving transmission and adaptation to bank voles (Myodes glareolus), we found that prions causing CWD in Norway induced incubation times, neuropathology, regional deposition of misfolded prion protein aggregates in the brain, and size of their protease-resistant core, different from those that characterize North American CWD. These findings show that CWD prion strains affecting Norwegian cervids are distinct from those found in North America, implying that the highly contagious North American CWD prions are not the proximate cause of the newly discovered Norwegian CWD cases. In addition, Norwegian CWD isolates showed an unexpected strain variability, with reindeer and moose being caused by different CWD strains. Our findings shed light on the origin of emergent European CWD, have significant implications for understanding the nature and the ecology of CWD in Europe, and highlight the need to assess the zoonotic potential of the new CWD strains detected in Europe.

Footnotes

↵¹To whom correspondence may be addressed. Email: romolo.nonno{at}iss.it.
↵²S.L.B. and U.A. contributed equally to this work.

Author contributions: R.N., G.C.T., S.L.B., and U.A. designed research; M.A.D.B., L.P., C.D., I.V., B.C., S.M., G.R., and L.T. performed research; T.V., J.V., K.M., G.M., and S.L.B. contributed new reagents/analytic tools; R.N., M.A.D.B., and L.P. analyzed data; and R.N. wrote the paper.
The authors declare no competing interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2013237117/-/DCSupplemental.