Canine D163-PrP polymorphic variant does not provide complete protection against prion infection in small ruminant PrP context

Alba Marín-Moreno,Patricia Aguilar-Calvo,Lorenzo González,Juan Carlos Espinosa,José Luis Pitarch,Natalia Fernández-Borges,Juan María Torres

doi:10.1038/s41598-021-93594-x

Alba Marín-Moreno, Patricia Aguilar-Calvo + Show 5 more

Open Access

https://doi.org/10.1038/s41598-021-93594-x

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Abstract

E/D163 polymorphism of dog prion protein (PrP) has been recently proposed as the variant responsible for canid prion resistance. To further investigate the protective role of this variant against prion replication, the transgenic mouse model OvPrP-Tg532 expressing sheep/goat PrP carrying the substitution D162 (equivalent to D163 position of dog PrP) was generated and intracranially inoculated with a broad collection of small ruminant prion strains. OvPrP-Tg532 mice showed resistance to classical bovine spongiform encephalopathy (BSE) from sheep and some classical scrapie isolates from sheep and goat but were susceptible to ovine atypical L-BSE and numerous classical scrapie isolates. Strikingly, some of these classical scrapie isolates showed a shift in their prion strain properties. These results suggest that other PrP residues apart from E/D163 variant of dog PrP or factors distinct than PrP may participate in prion resistance of canids and that different factors may be required for D162 sheep PrP to provide effective protection to sheep against ruminant prions.

Highlights

E/D163 polymorphism of dog prion protein (PrP) has been recently proposed as the variant responsible for canid prion resistance
This study further investigates the protective role exerted by the dog PrP D/E163 polymorphic variant in the sheep/goat PrP context towards prion replication
P rPC expression level was determined in brain homogenates of mice by serial dilution in western blotting (WB) and compared to OvPrP-Tg501 brain PrPC expression levels

Summary

Introduction

E/D163 polymorphism of dog prion protein (PrP) has been recently proposed as the variant responsible for canid prion resistance. OvPrP-Tg532 mice showed resistance to classical bovine spongiform encephalopathy (BSE) from sheep and some classical scrapie isolates from sheep and goat but were susceptible to ovine atypical L-BSE and numerous classical scrapie isolates. Some of these classical scrapie isolates showed a shift in their prion strain properties. These results suggest that other PrP residues apart from E/D163 variant of dog PrP or factors distinct than PrP may participate in prion resistance of canids and that different factors may be required for D162 sheep PrP to provide effective protection to sheep against ruminant prions. PrPSc suffers a change in its secondary structure, richer in β-sheet content Such transformation modifies the protein biochemical features. Animal prion diseases encompass scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME)[5] and camel prion disease (CPD)[6]

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