title: Disease-specific motifs can be identified in circulating nucleic acids from live elk and cattle infected with transmissible spongiform encephalopathies.
abstract: To gain insight into the disease progression of transmissible spongiform encephalopathies (TSE), we searched for disease-specific patterns in circulating nucleic acids (CNA) in elk and cattle. In a 25-month time-course experiment, CNAs were isolated from blood samples of 24 elk (Cervus elaphus) orally challenged with chronic wasting disease (CWD) infectious material. In a separate experiment, blood-sample CNAs from 29 experimental cattle (Bos taurus) 40 months post-inoculation with clinical bovine spongiform encephalopathy (BSE) were analyzed according to the same protocol. Next-generation sequencing provided broad elucidation of sample CNAs: we detected infection-specific sequences as early as 11 months in elk (i.e. at least 3 months before the appearance of the first clinical signs) and we established CNA patterns related to BSE in cattle at least 4 months prior to clinical signs. In elk, a progression of CNA sequence patterns was found to precede and correlate with macro-observable disease progression, including delayed CWD progression in elk with PrP genotype LM. Some of the patterns identified contain transcription-factor-binding sites linked to endogenous retroviral integration. These patterns suggest that retroviruses may be connected to the manifestation of TSEs. Our results may become useful for the early diagnosis of TSE in live elk and cattle.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, Sun Center of Excellence for Visual Genomics, University of Calgary, Calgary, AB, Canada T2N 4N1.
authors.forename: Paul M K
authors.initials: PM
authors.lastname: Gordon
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Schütz
authors.forename: Julia
authors.initials: J
authors.lastname: Beck
authors.forename: Howard B
authors.initials: HB
authors.lastname: Urnovitz
authors.forename: Catherine
authors.initials: C
authors.lastname: Graham
authors.forename: Renee
authors.initials: R
authors.lastname: Clark
authors.forename: Sandor
authors.initials: S
authors.lastname: Dudas
authors.forename: Stefanie
authors.initials: S
authors.lastname: Czub
authors.forename: Maria
authors.initials: M
authors.lastname: Sensen
authors.forename: Bertram
authors.initials: B
authors.lastname: Brenig
authors.forename: Martin H
authors.initials: MH
authors.lastname: Groschup
authors.forename: Robert B
authors.initials: RB
authors.lastname: Church
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Sensen
mesh_terms: D000818:Animals; D002417:Cattle; D004247:DNA / Q000097:blood*; D003670:Deer; D018450:Disease Progression; D016643:Encephalopathy, Bovine Spongiform / Q000097:blood / Q000175:diagnosis*; D005260:Female; D017422:Sequence Analysis, DNA; D034081:Wasting Disease, Chronic / Q000097:blood / Q000175:diagnosis*
chemical_list: D004247:DNA