Messenger RNA Biomarkers of Bovine Respiratory Syncytial Virus Infection in whole blood of dairy calves

Bovine Respiratory Syncytial Virus (BRSV) is a leading cause of Bovine Respiratory Disease (BRD) in young calves, which is responsible for substantial morbidity and mortality. Infection with BRSV induces global gene expression changes in respiratory tissues. If these changes are observed in tissues which are accessible in live animals, such as whole blood, they may be used as biomarkers of the disease. Therefore, the objective of the current study was to elucidate the whole blood transcriptomic response to an experimental challenge with BRSV, in dairy calves. Holstein-Friesian calves were either inoculated with virus (103.5 TCID50/ml x 15 ml) (n=12) or mock challenged with sterile phosphate buffered saline (n=6). Clinical signs were scored daily and whole blood was collected in Tempus RNA tubes immediately prior to euthanasia, at day 7 post-challenge. RNA was extracted from blood and sequenced (150 bp paired-end). Sequence reads were aligned to the UMD3.1 bovine reference genome and differential gene expression analysis was performed using EdgeR. An MDS plot displayed an obvious separation between BRSV challenged and control calves based on whole blood gene expression changes, despite an observed mild clinical manifestation of the disease. There were 281 differentially expressed (DE) genes (p < 0.05, FDR < 0.1, fold change > 2) between the BRSV challenged and control calves. The top enriched KEGG pathways and gene ontology terms were associated with viral infection and included “Influenza A”, “defense response to virus”, “regulation of viral life cycle” and “innate immune response”. Highly DE genes involved in these pathways are may be beneficial for the diagnosis of subclinical BRD from blood samples. Overall design: Examination of a single tissue type (whole blood) in two different treatment groups, BRSV challenged calves (n=12) and control calves (n=6)