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Whole blood transcriptomic analysis in BoHV-1 experimentally challenged dairy calves and comparison to a Bovine Respiratory Syncytial Virus (BRSV) challenge

ABSTRACT: Bovine Herpesvirus 1 (BoHV-1) is a leading cause of Bovine Respiratory Disease (BRD) in young calves, which is responsible for substantial morbidity and mortality. Therefore, the objective of the current study was to elucidate the whole blood mRNA transcriptomic response to an experimental challenge with BoHV-1, in dairy calves. Holstein-Friesian calves were either challenged by intranasal atomisation with BoHV1 virus (6.3 x 10^7/mL x 1.35mL) (n=12) or mock challenged with sterile phosphate buffered saline (n=6). Clinical signs were scored daily until euthanasia at day 6 post-challenge. Total RNA was extracted and sequenced from whole blood (100 bp paired-end). Sequence reads were aligned to the ARS-UCD1.2 bovine reference genome and differential gene expression analysis was performed using EdgeR. An MDS plot displayed an obvious separation between BoHV-1 challenged and control calves based on the gene expression changes in whole blood. There were 488 differentially expressed (DE) genes (p < 0.05, FDR < 0.1, fold change > 2) between the BoHV-1 challenged and control calves.

ORGANISM(S): Bos taurus

PROVIDER: GSE199108 | GEO | 2022/08/19

REPOSITORIES: GEO

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Project description:Bovine Respiratory Disease (BRD) is responsible for the majority of calf morbidity and mortality. One of the main causes of BRD is initial infection with Bovine Respiratory Syncytial Virus (BRSV). The objective of this study was to elucidate the changes in the host's bronchial lymph node miRNA transcriptome in response to BRSV in a controlled viral challenge. Holstein-Friesian calves were either inoculated with BRSV (103.5 TCID50/ml x 15 ml) (n=12) or mock challenged with phosphate buffered saline (n=6). Clinical signs were scored daily until euthanasia at day 7 post-challenge. Total RNA was extracted and sequenced (75 bp) from bronchial lymph nodes. Sequences were filtered for contaminant short RNA species, and subsequently read counts for known miRNAS were generated using the miRDeep2 package with the UMD 3.1 version of the genome and the bovine mature miRNA sequences from the miRBase database (release 22). EdgeR was used for differential expression analysis and Targetscan was used to identify target genes for the differentially expressed (DE) miRNAs. Pathway and gene ontology analyses on target genes were carried out using Ingenuity Pathway analysis (Qiagen). There was a clear separation between BRSV challenged and control calves based on miRNA gene expression changes, despite an observed mild clinical manifestation of the disease. There were 119 DE miRNAs (p<0.05, FDR<0.1, fold change>1.5) between the BRSV challenged and control calves. The DE miRNAs were predicted to target 465 genes which were previously found to be DE in bronchial lymph node tissue, between these BRSV challenged and control calves. Out of the DE predicted target genes, 455 genes had inverse fold changes to that of the DE miRNAs. There were 8 enriched pathways among the DE predicted target genes with inverse fold changes to that of the DE miRNA including: granulocyte and agranulocyte adhesion and diapedesis, interferon signaling and role of pathogen recognition receptors in recognition of bacteria and viruses. Functions predicted to be increased included: T cell response, apoptosis of leukocytes, immune response of cells and stimulation of cells. Pathogen recognition and proliferation of cytotoxic T cells are vital for the recognition and subsequent elimination of the virus.

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Whole blood transcriptomic analysis in BoHV-1 experimentally challenged dairy calves and comparison to a Bovine Respiratory Syncytial Virus (BRSV) challenge

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