Neural transcriptomic signature of chronic wasting disease in white-tailed deer

Eóin O’Hara,Debbie Mckenzie,Allen Herbst,Judd M Aiken,Pamela Skinner,Paul Stothard,Arun Kommadath,Negin Goodarzi

doi:10.1186/s12864-022-08306-0

Abstract

BackgroundThe increasing prevalence and expanding geographical range of the chronic wasting disease (CWD) panzootic in cervids is threatening human, animal, environmental and economic health. The pathogenesis of CWD in cervids is, however, not well understood. We used RNA sequencing (RNA-seq) to compare the brain transcriptome from white-tailed deer (WTD; Odocoileus virginianus) clinically affected with CWD (n = 3) to WTD that tested negative (n = 8) for CWD. In addition, one preclinical CWD+ brain sample was analyzed by RNA-seq.ResultsWe found 255 genes that were significantly deregulated by CWD, 197 of which were upregulated. There was a high degree of overlap in differentially expressed genes (DEGs) identified when using either/both the reference genome assembly of WTD for mapping sequenced reads to or the better characterized genome assembly of a closely related model species, Bos taurus. Quantitative PCR of a subset of the DEGs confirmed the RNA-seq data. Gene ontology term enrichment analysis found a majority of genes involved in immune activation, consistent with the neuroinflammatory pathogenesis of prion diseases. A metagenomic analysis of the RNA-seq data was conducted to look for the presence of spiroplasma and other bacteria in CWD infected deer brain tissue.ConclusionsThe gene expression changes identified highlight the role of innate immunity in prion infection, potential disease associated biomarkers and potential targets for therapeutic agents. An association between CWD and spiroplasma infection was not found.

Highlights

Chronic wasting disease (CWD) is a naturally occurring, universally fatal prion disease or transmissible spongiform encephalopathy (TSE) of cervids [1]
Deer brain samples Deer brain tissue was obtained at necropsy from one uninfected and three clinically-affected white-tailed deer (WTD) that had been orally infected with Wisc-1 prions [12]
Additional deer brain samples were obtained from hunter-harvested WTD (Wisconsin, chronic wasting disease (CWD) test negative, n = 3) and from a Saskatchewan white-tail deer herd depopulated for CWD control (n = 4)

Summary

Introduction

Chronic wasting disease (CWD) is a naturally occurring, universally fatal prion disease or transmissible spongiform encephalopathy (TSE) of cervids (e.g. deer, moose, elk) [1]. First described in captive Colorado mule deer in 1967, the disease is found in farmed and free-ranging cervid populations across North America, with additional cases documented in Scandinavia and South Korea [2]. The prevalence of CWD can be very high, above 50% in some free-ranging populations and 90% in some captive herds. Migration of the infectious prions to the nervous system results in full brain involvement and clinical disease and involves widespread deposition of PrPCWD in numerous brain areas, but especially the obex, superior colliculus, hypothalamus, septal nucleus of the basal ganglia and cerebellum [5]. The increasing prevalence and expanding geographical range of the chronic wasting disease (CWD) panzootic in cervids is threatening human, animal, environmental and economic health. One preclinical CWD+ brain sample was analyzed by RNA-seq

Methods

Results

Conclusion