Cargando…

Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic Wasting Disease Strains

Transmission of chronic wasting disease (CWD) between cervids is influenced by the primary structure of the host cellular prion protein (PrP(C)). In white-tailed deer, PRNP alleles encode the polymorphisms Q95 G96 (wild type [wt]), Q95 S96 (referred to as the S96 allele), and H95 G96 (referred to as...

Descripción completa

Detalles Bibliográficos
Autores principales: Duque Velásquez, Camilo, Kim, Chiye, Herbst, Allen, Daude, Nathalie, Garza, Maria Carmen, Wille, Holger, Aiken, Judd, McKenzie, Debbie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665243/
https://www.ncbi.nlm.nih.gov/pubmed/26423950
http://dx.doi.org/10.1128/JVI.02010-15
_version_ 1782403551149948928
author Duque Velásquez, Camilo
Kim, Chiye
Herbst, Allen
Daude, Nathalie
Garza, Maria Carmen
Wille, Holger
Aiken, Judd
McKenzie, Debbie
author_facet Duque Velásquez, Camilo
Kim, Chiye
Herbst, Allen
Daude, Nathalie
Garza, Maria Carmen
Wille, Holger
Aiken, Judd
McKenzie, Debbie
author_sort Duque Velásquez, Camilo
collection PubMed
description Transmission of chronic wasting disease (CWD) between cervids is influenced by the primary structure of the host cellular prion protein (PrP(C)). In white-tailed deer, PRNP alleles encode the polymorphisms Q95 G96 (wild type [wt]), Q95 S96 (referred to as the S96 allele), and H95 G96 (referred to as the H95 allele), which differentially impact CWD progression. We hypothesize that the transmission of CWD prions between deer expressing different allotypes of PrP(C) modifies the contagious agent affecting disease spread. To evaluate the transmission properties of CWD prions derived experimentally from deer of four PRNP genotypes (wt/wt, S96/wt, H95/wt, or H95/S96), transgenic (tg) mice expressing the wt allele (tg33) or S96 allele (tg60) were challenged with these prion agents. Passage of deer CWD prions into tg33 mice resulted in 100% attack rates, with the CWD H95/S96 prions having significantly longer incubation periods. The disease signs and neuropathological and protease-resistant prion protein (PrP-res) profiles in infected tg33 mice were similar between groups, indicating that a prion strain (Wisc-1) common to all CWD inocula was amplified. In contrast, tg60 mice developed prion disease only when inoculated with the H95/wt and H95/S96 CWD allotypes. Serial passage in tg60 mice resulted in adaptation of a novel CWD strain (H95(+)) with distinct biological properties. Transmission of first-passage tg60CWD-H95(+) isolates into tg33 mice, however, elicited two prion disease presentations consistent with a mixture of strains associated with different PrP-res glycotypes. Our data indicate that H95-PRNP heterozygous deer accumulated two CWD strains whose emergence was dictated by the PrP(C) primary structure of the recipient host. These findings suggest that CWD transmission between cervids expressing distinct PrP(C) molecules results in the generation of novel CWD strains. IMPORTANCE CWD prions are contagious among wild and captive cervids in North America and in South Korea. We present data linking the amino acid variant Q95H in white-tailed deer cellular prion protein (PrP(C)) to the emergence of a novel CWD strain (H95(+)). We show that, upon infection, deer expressing H95-PrP(C) molecules accumulated a mixture of CWD strains that selectively propagated depending on the PRNP genotype of the host in which they were passaged. Our study also demonstrates that mice expressing the deer S96-PRNP allele, previously shown to be resistant to various cervid prions, are susceptible to H95(+) CWD prions. The potential for the generation of novel strains raises the possibility of an expanded host range for CWD.
format Online
Article
Text
id pubmed-4665243
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher American Society for Microbiology
record_format MEDLINE/PubMed
spelling pubmed-46652432015-12-10 Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic Wasting Disease Strains Duque Velásquez, Camilo Kim, Chiye Herbst, Allen Daude, Nathalie Garza, Maria Carmen Wille, Holger Aiken, Judd McKenzie, Debbie J Virol Prions Transmission of chronic wasting disease (CWD) between cervids is influenced by the primary structure of the host cellular prion protein (PrP(C)). In white-tailed deer, PRNP alleles encode the polymorphisms Q95 G96 (wild type [wt]), Q95 S96 (referred to as the S96 allele), and H95 G96 (referred to as the H95 allele), which differentially impact CWD progression. We hypothesize that the transmission of CWD prions between deer expressing different allotypes of PrP(C) modifies the contagious agent affecting disease spread. To evaluate the transmission properties of CWD prions derived experimentally from deer of four PRNP genotypes (wt/wt, S96/wt, H95/wt, or H95/S96), transgenic (tg) mice expressing the wt allele (tg33) or S96 allele (tg60) were challenged with these prion agents. Passage of deer CWD prions into tg33 mice resulted in 100% attack rates, with the CWD H95/S96 prions having significantly longer incubation periods. The disease signs and neuropathological and protease-resistant prion protein (PrP-res) profiles in infected tg33 mice were similar between groups, indicating that a prion strain (Wisc-1) common to all CWD inocula was amplified. In contrast, tg60 mice developed prion disease only when inoculated with the H95/wt and H95/S96 CWD allotypes. Serial passage in tg60 mice resulted in adaptation of a novel CWD strain (H95(+)) with distinct biological properties. Transmission of first-passage tg60CWD-H95(+) isolates into tg33 mice, however, elicited two prion disease presentations consistent with a mixture of strains associated with different PrP-res glycotypes. Our data indicate that H95-PRNP heterozygous deer accumulated two CWD strains whose emergence was dictated by the PrP(C) primary structure of the recipient host. These findings suggest that CWD transmission between cervids expressing distinct PrP(C) molecules results in the generation of novel CWD strains. IMPORTANCE CWD prions are contagious among wild and captive cervids in North America and in South Korea. We present data linking the amino acid variant Q95H in white-tailed deer cellular prion protein (PrP(C)) to the emergence of a novel CWD strain (H95(+)). We show that, upon infection, deer expressing H95-PrP(C) molecules accumulated a mixture of CWD strains that selectively propagated depending on the PRNP genotype of the host in which they were passaged. Our study also demonstrates that mice expressing the deer S96-PRNP allele, previously shown to be resistant to various cervid prions, are susceptible to H95(+) CWD prions. The potential for the generation of novel strains raises the possibility of an expanded host range for CWD. American Society for Microbiology 2015-09-30 /pmc/articles/PMC4665243/ /pubmed/26423950 http://dx.doi.org/10.1128/JVI.02010-15 Text en Copyright © 2015 Duque Velásquez et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Prions
Duque Velásquez, Camilo
Kim, Chiye
Herbst, Allen
Daude, Nathalie
Garza, Maria Carmen
Wille, Holger
Aiken, Judd
McKenzie, Debbie
Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic Wasting Disease Strains
title Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic Wasting Disease Strains
title_full Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic Wasting Disease Strains
title_fullStr Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic Wasting Disease Strains
title_full_unstemmed Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic Wasting Disease Strains
title_short Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic Wasting Disease Strains
title_sort deer prion proteins modulate the emergence and adaptation of chronic wasting disease strains
topic Prions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665243/
https://www.ncbi.nlm.nih.gov/pubmed/26423950
http://dx.doi.org/10.1128/JVI.02010-15
work_keys_str_mv AT duquevelasquezcamilo deerprionproteinsmodulatetheemergenceandadaptationofchronicwastingdiseasestrains
AT kimchiye deerprionproteinsmodulatetheemergenceandadaptationofchronicwastingdiseasestrains
AT herbstallen deerprionproteinsmodulatetheemergenceandadaptationofchronicwastingdiseasestrains
AT daudenathalie deerprionproteinsmodulatetheemergenceandadaptationofchronicwastingdiseasestrains
AT garzamariacarmen deerprionproteinsmodulatetheemergenceandadaptationofchronicwastingdiseasestrains
AT willeholger deerprionproteinsmodulatetheemergenceandadaptationofchronicwastingdiseasestrains
AT aikenjudd deerprionproteinsmodulatetheemergenceandadaptationofchronicwastingdiseasestrains
AT mckenziedebbie deerprionproteinsmodulatetheemergenceandadaptationofchronicwastingdiseasestrains