Post by kirbydoc on Jan 25, 2023 20:27:27 GMT -5
Novel Prion Strain as Cause of Chronic Wasting Disease in a Moose, Finland
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Julianna L. Sun, Sehun Kim, Jenna Crowell, Bailey K. Webster, Emma K. Raisley, Diana C. Lowe, Jifeng Bian, Sirkka-Liisa Korpenfelt, Sylvie L. Benestad, and Glenn C. TellingComments to Author
Author affiliations: Colorado State University, Fort Collins, Colorado, USA (J.L. Sun, S. Kim, J. Crowell, B.K. Webster, E.K. Raisley, D.C. Lowe, J. Bian, G.C. Telling); Finnish Food Authority, Helsinki, Finland (S.-L. Korpenfelt); Norwegian Veterinary Institute, Ås, Norway (S.L. Benestad)
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Abstract
Our previous studies using gene-targeted mouse models of chronic wasting disease (CWD) demonstrated that Norway and North America cervids are infected with distinct prion strains that respond differently to naturally occurring amino acid variation at residue 226 of the prion protein. Here we performed transmissions in gene-targeted mice to investigate the properties of prions causing newly emergent CWD in moose in Finland. Although CWD prions from Finland and Norway moose had comparable responses to primary structural differences at residue 226, other distinctive criteria, including transmission kinetics, patterns of neuronal degeneration, and conformational features of prions generated in the brains of diseased mice, demonstrated that the strain properties of Finland moose CWD prions are different from those previously characterized in Norway CWD. Our findings add to a growing body of evidence for a diverse portfolio of emergent strains in Nordic countries that are etiologically distinct from the comparatively consistent strain profile of North America CWD.
Prions are infectious proteins that cause fatal, incurable neurodegenerative diseases of humans and animals, which include Creutzfeldt-Jakob disease (CJD), sheep scrapie, bovine spongiform encephalopathy, and chronic wasting disease (CWD) of cervids. The extraordinary biology and transmissibility of these disorders stems from the protean conformational properties of the prion protein (PrP). Although the secondary structure of host-encoded cellular PrP (PrPC) is predominantly α-helical, during disease its relatively underglycosylated infectious counterpart (PrPSc) assembles into amyloid fibrils with parallel, in-register, intermolecular β-sheets (1–7). The replicative properties of prions stem from the capacity of PrPSc to template its conformation on PrPC in a cyclical process resulting in exponential accumulation of prion infectivity (8–11).
Although they lack nucleic acids, prions exhibit heritable strain properties that influence disease outcomes, including the time between infection and disease onset (incubation period), clinical signs, patterns of neuronal degeneration and PrPSc deposition in the central nervous system (CNS), and the ability to replicate in non-CNS tissues such as the lymphoreticular system and musculature (12). Strain properties also influence the capacity of prions from one species to cause disease in a different species (13). Heritable strain information appears to be enciphered by distinct PrPSc conformations that are faithfully propagated during prion replication (14,15).
The food-chain transmission of bovine spongiform encephalopathy prions that resulted in a variant form of CJD illustrates the unpredictable potential of emergent strains for zoonotic transmission (13). Although novel prion diseases and strain variants continue to arise in increasing numbers of animal species, CWD elicits particular concern (16). After its initial description in a captive deer facility (17), uncontrolled contagious transmission has resulted in growing numbers of CWD-affected cervids in at least 30 US states and 3 Canada provinces (18). Inadvertent importation of subclinically diseased animals from North America led to the establishment of CWD in South Korea (19–21). CWD was also diagnosed in free-ranging Norwegian reindeer in 2016 (22), and additional cases were subsequently identified in growing numbers of moose, red deer, and reindeer from Norway, Sweden, and Finland (23).
On This Page
Materials and Methods Results Discussion Cite This Article
Julianna L. Sun, Sehun Kim, Jenna Crowell, Bailey K. Webster, Emma K. Raisley, Diana C. Lowe, Jifeng Bian, Sirkka-Liisa Korpenfelt, Sylvie L. Benestad, and Glenn C. TellingComments to Author
Author affiliations: Colorado State University, Fort Collins, Colorado, USA (J.L. Sun, S. Kim, J. Crowell, B.K. Webster, E.K. Raisley, D.C. Lowe, J. Bian, G.C. Telling); Finnish Food Authority, Helsinki, Finland (S.-L. Korpenfelt); Norwegian Veterinary Institute, Ås, Norway (S.L. Benestad)
Cite This Article
Abstract
Our previous studies using gene-targeted mouse models of chronic wasting disease (CWD) demonstrated that Norway and North America cervids are infected with distinct prion strains that respond differently to naturally occurring amino acid variation at residue 226 of the prion protein. Here we performed transmissions in gene-targeted mice to investigate the properties of prions causing newly emergent CWD in moose in Finland. Although CWD prions from Finland and Norway moose had comparable responses to primary structural differences at residue 226, other distinctive criteria, including transmission kinetics, patterns of neuronal degeneration, and conformational features of prions generated in the brains of diseased mice, demonstrated that the strain properties of Finland moose CWD prions are different from those previously characterized in Norway CWD. Our findings add to a growing body of evidence for a diverse portfolio of emergent strains in Nordic countries that are etiologically distinct from the comparatively consistent strain profile of North America CWD.
Prions are infectious proteins that cause fatal, incurable neurodegenerative diseases of humans and animals, which include Creutzfeldt-Jakob disease (CJD), sheep scrapie, bovine spongiform encephalopathy, and chronic wasting disease (CWD) of cervids. The extraordinary biology and transmissibility of these disorders stems from the protean conformational properties of the prion protein (PrP). Although the secondary structure of host-encoded cellular PrP (PrPC) is predominantly α-helical, during disease its relatively underglycosylated infectious counterpart (PrPSc) assembles into amyloid fibrils with parallel, in-register, intermolecular β-sheets (1–7). The replicative properties of prions stem from the capacity of PrPSc to template its conformation on PrPC in a cyclical process resulting in exponential accumulation of prion infectivity (8–11).
Although they lack nucleic acids, prions exhibit heritable strain properties that influence disease outcomes, including the time between infection and disease onset (incubation period), clinical signs, patterns of neuronal degeneration and PrPSc deposition in the central nervous system (CNS), and the ability to replicate in non-CNS tissues such as the lymphoreticular system and musculature (12). Strain properties also influence the capacity of prions from one species to cause disease in a different species (13). Heritable strain information appears to be enciphered by distinct PrPSc conformations that are faithfully propagated during prion replication (14,15).
The food-chain transmission of bovine spongiform encephalopathy prions that resulted in a variant form of CJD illustrates the unpredictable potential of emergent strains for zoonotic transmission (13). Although novel prion diseases and strain variants continue to arise in increasing numbers of animal species, CWD elicits particular concern (16). After its initial description in a captive deer facility (17), uncontrolled contagious transmission has resulted in growing numbers of CWD-affected cervids in at least 30 US states and 3 Canada provinces (18). Inadvertent importation of subclinically diseased animals from North America led to the establishment of CWD in South Korea (19–21). CWD was also diagnosed in free-ranging Norwegian reindeer in 2016 (22), and additional cases were subsequently identified in growing numbers of moose, red deer, and reindeer from Norway, Sweden, and Finland (23).
The development and application of genetically modified, CWD-susceptible mice expressing cervid PrPC (CerPrPC) has provided insights into multiple aspects of pathogenesis, including the impact of naturally occurring PRNP coding sequence variations (16). Whereas North America deer and moose encode glutamine (Q) at codon 226 (CerPrP-Q226), North America elk encode glutamate (E) at this position (CerPrP-E226). Early studies in transgenic (Tg) mice suggested a role for this variation in the selection and propagation of CWD strains (24–26). To precisely assess the effects of this primary structural difference, we created CWD-susceptible gene-targeted (Gt) mice in which the PrP coding sequence was replaced with CerPrP-Q226 or CerPrP-E226 (27). Because the resulting mice, referred to as GtQ and GtE mice, express equivalent, physiologically controlled levels of CerPrPC and are otherwise syngeneic, we were able to ascribe distinct disease outcomes in each line to the effects of these amino acids (27). Furthermore, in contrast to previous CWD-susceptible Tg mice, Gt mice recapitulated the lymphotropic properties of CWD strains (27,28). By using Gt mice, we showed that emergent strains causing CWD in Norway reindeer and moose were unrelated to established North America forms of CWD and that they responded differently to variation at residue 226 (28). These findings underscored the utility of Gt mice for accurately defining the strain properties of emergent CWD prions (28). The goal of this study was to characterize a newly emergent form of CWD in Finland moose.
For more detailed information see: Moose with Prions in Finland