title: Whole Blood Gene Expression Profiling in Preclinical and Clinical Cattle Infected with Atypical Bovine Spongiform Encephalopathy.
abstract: Prion diseases, such as bovine spongiform encephalopathies (BSE), are transmissible neurodegenerative disorders affecting humans and a wide variety of mammals. Variant Creutzfeldt-Jakob disease (vCJD), a prion disease in humans, has been linked to exposure to BSE prions. This classical BSE (cBSE) is now rapidly disappearing as a result of appropriate measures to control animal feeding. Besides cBSE, two atypical forms (named H- and L-type BSE) have recently been described in Europe, Japan, and North America. Here we describe the first wide-spectrum microarray analysis in whole blood of atypical BSE-infected cattle. Transcriptome changes in infected animals were analyzed prior to and after the onset of clinical signs. The microarray analysis revealed gene expression changes in blood prior to the appearance of the clinical signs and during the progression of the disease. A set of 32 differentially expressed genes was found to be in common between clinical and preclinical stages and showed a very similar expression pattern in the two phases. A 22-gene signature showed an oscillating pattern of expression, being differentially expressed in the preclinical stage and then going back to control levels in the symptomatic phase. One gene, SEL1L3, was downregulated during the progression of the disease. Most of the studies performed up to date utilized various tissues, which are not suitable for a rapid analysis of infected animals and patients. Our findings suggest the intriguing possibility to take advantage of whole blood RNA transcriptional profiling for the preclinical identification of prion infection. Further, this study highlighted several pathways, such as immune response and metabolism that may play an important role in peripheral prion pathogenesis. Finally, the gene expression changes identified in the present study may be further investigated as a fingerprint for monitoring the progression of disease and for developing targeted therapeutic interventions.
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA), Functional and Structural Genomics sector, Trieste, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Xerxa
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA), Functional and Structural Genomics sector, Trieste, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Barbisin
authors.affiliation: Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d'Aosta, Torino, Italy.
authors.forename: Maria Novella
authors.initials: MN
authors.lastname: Chieppa
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA), Functional and Structural Genomics sector, Trieste, Italy.
authors.forename: Helena
authors.initials: H
authors.lastname: Krmac
authors.affiliation: Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d'Aosta, Torino, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Vallino Costassa
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA), Functional and Structural Genomics sector, Trieste, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vatta
authors.affiliation: Pathology Department, Animal and Plant Health Agency (Weybridge), New Haw, Addlestone, United Kingdom.
authors.forename: Marion
authors.initials: M
authors.lastname: Simmons
authors.affiliation: Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d'Aosta, Torino, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Caramelli
authors.affiliation: Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d'Aosta, Torino, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Casalone
authors.affiliation: Istituto Zooprofilattico Sperimentale del Piemonte Liguria e Valle d'Aosta, Torino, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Corona
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA), Functional and Structural Genomics sector, Trieste, Italy.
authors.forename: Giuseppe
authors.identifier: http://orcid.org/0000-0003-0716-4393
authors.initials: G
authors.lastname: Legname
mesh_terms: D000818:Animals; D002417:Cattle; D018450:Disease Progression; D015536:Down-Regulation; D016643:Encephalopathy, Bovine Spongiform / Q000097:blood / Q000235:genetics*; D020869:Gene Expression Profiling; D011506:Proteins / Q000235:genetics; D059467:Transcriptome
chemical_list: D011506:Proteins