Elucidation of the host transcriptomic response to bovine respiratory syncytial virus

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in calves over one month of age. In a controlled challenge study in artificially-reared dairy calves, the influence of the host response to bovine respiratory syncytial virus (BRSV) was examined. Holstein-Friesian calves were either inoculated with BRSV (10^5/ml × 15 ml/animal) (n=12) or mock challenged with phosphate buffer saline (10ml/animal) (n=6). Calves were euthanised on day 7 post-challenge. Bronchial lymph nodes were collected; RNA was extracted and sequenced (75bp paired-end). Sequenced reads were adapter trimmed, quality assessed (FastQC) and aligned to the bovine genome (UMD 3.1) using STAR. Differential gene expression analysis was performed using EdgeR, and pathway and gene ontology analyses were carried out using g:Profiler, IPA and DAVID. There was a clear separation between BRSV challenged and control calves based on log2 fold gene expression changes, despite an observed mild clinical manifestation of the disease. There were 934 differentially expressed genes (DEG) (p < 0.05, FDR < 0.1, fold change > 2) between the BRSV challenged and control calves. Over-represented gene ontology terms, pathways and molecular functions, among the DEG, were associated with immune responses and defense responses to a virus. Overall design: Bronchial lymph node tissues were collected for RNA-Seq analysis from 18 calves (12 BRSV challenged and 6 controls).