scholarly journals Adaptive selection of a prion strain conformer corresponding to established North American CWD during propagation of novel emergent Norwegian strains in mice expressing elk or deer prion protein

2021 ◽  
Vol 17 (7) ◽  
pp. e1009748
Author(s):  
Jifeng Bian ◽  
Sehun Kim ◽  
Sarah J. Kane ◽  
Jenna Crowell ◽  
Julianna L. Sun ◽  
...  

Prions are infectious proteins causing fatal, transmissible neurodegenerative diseases of animals and humans. Replication involves template-directed refolding of host encoded prion protein, PrPC, by its infectious conformation, PrPSc. Following its discovery in captive Colorado deer in 1967, uncontrollable contagious transmission of chronic wasting disease (CWD) led to an expanded geographic range in increasing numbers of free-ranging and captive North American (NA) cervids. Some five decades later, detection of PrPSc in free-ranging Norwegian (NO) reindeer and moose marked the first indication of CWD in Europe. To assess the properties of these emergent NO prions and compare them with NA CWD we used transgenic (Tg) and gene targeted (Gt) mice expressing PrP with glutamine (Q) or glutamate (E) at residue 226, a variation in wild type cervid PrP which influences prion strain selection in NA deer and elk. Transmissions of NO moose and reindeer prions to Tg and Gt mice recapitulated the characteristic features of CWD in natural hosts, revealing novel prion strains with disease kinetics, neuropathological profiles, and capacities to infect lymphoid tissues and cultured cells that were distinct from those causing NA CWD. In support of strain variation, PrPSc conformers comprising emergent NO moose and reindeer CWD were subject to selective effects imposed by variation at residue 226 that were different from those controlling established NA CWD. Transmission of particular NO moose CWD prions in mice expressing E at 226 resulted in selection of a kinetically optimized conformer, subsequent transmission of which revealed properties consistent with NA CWD. These findings illustrate the potential for adaptive selection of strain conformers with improved fitness during propagation of unstable NO prions. Their potential for contagious transmission has implications for risk analyses and management of emergent European CWD. Finally, we found that Gt mice expressing physiologically controlled PrP levels recapitulated the lymphotropic properties of naturally occurring CWD strains resulting in improved susceptibilities to emergent NO reindeer prions compared with over-expressing Tg counterparts. These findings underscore the refined advantages of Gt models for exploring the mechanisms and impacts of strain selection in peripheral compartments during natural prion transmission.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Edoardo Bistaffa ◽  
Tram Thu Vuong ◽  
Federico Angelo Cazzaniga ◽  
Linh Tran ◽  
Giulia Salzano ◽  
...  

AbstractChronic wasting disease (CWD) is a highly contagious prion disease affecting captive and free-ranging cervid populations. CWD has been detected in United States, Canada, South Korea and, most recently, in Europe (Norway, Finland and Sweden). Animals with CWD release infectious prions in the environment through saliva, urine and feces sustaining disease spreading between cervids but also potentially to other non-cervids ruminants (e.g. sheep, goats and cattle). In the light of these considerations and due to CWD unknown zoonotic potential, it is of utmost importance to follow specific surveillance programs useful to minimize disease spreading and transmission. The European community has already in place specific surveillance measures, but the traditional diagnostic tests performed on nervous or lymphoid tissues lack sensitivity. We have optimized a Real-Time Quaking-Induced Conversion (RT-QuIC) assay for detecting CWD prions with high sensitivity and specificity to try to overcome this problem. In this work, we show that bank vole prion protein (PrP) is an excellent substrate for RT-QuIC reactions, enabling the detection of trace-amounts of CWD prions, regardless of prion strain and cervid species. Beside supporting the traditional diagnostic tests, this technology could be exploited for detecting prions in peripheral tissues from live animals, possibly even at preclinical stages of the disease.


PIERS Online ◽  
2007 ◽  
Vol 3 (1) ◽  
pp. 106-110
Author(s):  
Shaogang Wang ◽  
Xinpu Guan ◽  
Dangwei Wang ◽  
Xingyi Ma ◽  
Yi Su

Foods ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1914
Author(s):  
Scott Lafontaine ◽  
Kay Senn ◽  
Laura Knoke ◽  
Christian Schubert ◽  
Johanna Dennenlöhr ◽  
...  

Forty-two commercial non-alcoholic beer (NAB) brands were analyzed using sensory and chemical techniques to understand which analytes and/or flavors were most responsible for invoking the perception of “beer flavor” (for Northern Californian consumers). The aroma and taste profiles of the commercial NABs, a commercial soda, and a carbonated seltzer water (n = 44) were characterized using replicated descriptive and CATA analyses performed by a trained sensory panel (i.e., 11 panelists). A number of non-volatile and volatile techniques were then used to chemically deconstruct the products. Consumer analysis (i.e., 129 Northern Californian consumers) was also used to evaluate a selection of these NABs (i.e., 12) and how similar they thought the aroma, taste and mouthfeels of these products were to beer, soda, and water. The results show that certain constituents drive the aroma and taste profiles which are responsible for invoking beer perception for these North American consumers. Further, beer likeness might not be a driver of preference in this diverse beverage class for Northern Californian consumers. These are important insights for brewers planning to create products for similar markets and/or more broadly for companies interested in designing other functional/alternative food and beverage products.


Author(s):  
Santiago De-Luxan-Hernandez ◽  
Detlev Marpe ◽  
Heiko Schwarz ◽  
Klaus-Robert Muller ◽  
Mathias Wien ◽  
...  

2012 ◽  
Vol 48 (1) ◽  
pp. 197-214 ◽  
Author(s):  
H. Benoudnine ◽  
M. Keche ◽  
A. Ouamri ◽  
M. S. Woolfson

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