Caprine PrP variants harboring Asp-146, His-154 and Gln-211 alleles display reduced convertibility upon interaction with pathogenic murine prion protein in scrapie infected cells. Issue 5 (2nd September 2016)

• Record Type: Journal Article
• Authors: Kanata, Eirini; Arsenakis, Minas; Sklaviadis, Theodoros
• Is Part Of: Prion. Volume 10:Issue 5(2016)
• Page Start: 391
• Page End: 408
• Publication Date: 2016-09-02
• Subjects: 22LN2a#58 -- cell culture -- genotyping -- goats -- polymorphisms -- resistance -- Scrapie; Protein folding -- Periodicals; Prions -- Periodicals; Proteins -- Biotechnology -- Periodicals; 572.633
• DOI: 10.1080/19336896.2016.1199312
• Languages: English
• ISSNs: 1933-6896

Abstract

ABSTRACT: Scrapie, the prion disease of sheep and goats, is a devastating malady of small ruminants. Due to its infectious nature, epidemic outbreaks may occur in flocks/herds consisting of highly susceptible animals. Field studies identified scrapie-protective caprine PrP variants, harboring specific single amino acid changes (Met-142, Arg-143, Asp-146, Ser-146, His-154, Gln-211 and Lys-222). Their effects are under further evaluation, and aim to determine the most protective allele. We assessed some of these variants (Asp-146, His-154, Gln-211 and Lys-222), after their exogenous expression as murine-caprine chimeras in a scrapie- infected murine cell line. We report that exogenously expressed PrPs undergo conformational conversion upon interaction with the endogenous pathological murine prion protein (PrP SC ), which results in the detection of goat-specific and partially PK-resistant moieties. These moieties display a PK-resistance pattern distinct from the one detected in natural goat scrapie cases. Within this cellular model, distinct conformational conversion potentials were assigned to the tested variants. Molecules carrying the Asp-146, His-154 and Gln-211 alleles showed significantly lower conversion levels compared to wild type, confirming their protective effects against scrapie. Although we utilized a heterologous conversion system, this is to our knowledge, the first study of caprine PrP variants in a cellular context of scrapie, that confirms the protective effects of some of the studied alleles.