Assessment of IgE response and cytokine gene expression in pulmonary efferent lymph collected after ovalbumin inhalation during experimental infection of calves with bovine respiratory syncytial virus

Bovine Respiratory Syncytial virus (BRSV) is one of the major infectious agents in the etiology of the bovine respiratory disease complex. BRSV causes a respiratory syndrome in calves, which is associated with severe bronchiolitis. In this study we describe the effect of treatment with antiviral fusion protein inhibitor (FPI) and ibuprofen, on gene expression in lung tissue of calves infected with BRSV. Calves infected with BRSV are an excellent model of human RSV in infants: we hypothesized that FPI in combination with ibuprofen would provide the best therapeutic intervention for both species. The following experimental treatment groups of BRSV infected calves were used: 1) ibuprofen day 3–10, 2) ibuprofen day 5–10, 3) placebo, 4) FPI day 5–10, 5) FPI and ibuprofen day 5–10, 6) FPI and ibuprofen day 3–10. All calves were infected with BRSV on day 0. Daily clinical evaluation with monitoring of virus shedding by qRT-PCR was conducted. On day10 lung tissue with lesions (LL) and non-lesional (LN) was collected at necropsy, total RNA extracted, and RNA sequencing performed. Differential gene expression analysis was conducted with Gene ontology (GO) and KEGG pathway enrichment analysis. The most significant differential gene expression in BRSV infected lung tissues was observed in the comparison of LL with LN; oxidative stress and cell damage was especially noticeable. Innate and adaptive immune functions were reduced in LL. As expected, combined treatment with FPI and Ibuprofen, when started early, made the most difference in gene expression patterns in comparison with placebo, especially in pathways related to the innate and adaptive immune response in both LL and LN. Ibuprofen, when used alone, negatively affected the antiviral response and caused higher virus loads as shown by increased viral shedding. In contrast, when used with FPI Ibuprofen enhanced the specific antiviral effect of FPI, due to its ability to reduce the damaging effect of prostanoids and oxidative stress.

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Cytokine gene expression in aborting and non-aborting dams and in their foetuses after experimental infection with Neospora caninum at 110 days of gestation

Veterinary Parasitology ◽

10.1016/j.vetpar.2016.08.006 ◽

2016 ◽

Vol 227 ◽

pp. 138-142 ◽

Cited By ~ 9

Author(s):

S. Almeria ◽

B. Serrano-Pérez ◽

L. Darwich ◽

R. Mur-Novales ◽

I. Garcia-Ispierto ◽

...

Keyword(s):

Gene Expression ◽

Experimental Infection ◽

Neospora Caninum ◽

Cytokine Gene Expression ◽

Cytokine Gene

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An experimental infection model for reproduction of calf pneumonia with bovine respiratory syncytial virus (BRSV) based on one combined exposure of calves

Research in Veterinary Science ◽

10.1016/s0034-5288(02)00154-6 ◽

2003 ◽

Vol 74 (1) ◽

pp. 55-65 ◽

Cited By ~ 19

Author(s):

K Tjørnehøj ◽

Å Uttenthal ◽

B Viuff ◽

L.E Larsen ◽

C Røntved ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Experimental Infection ◽

Bovine Respiratory Syncytial Virus ◽

Infection Model ◽

Combined Exposure ◽

Syncytial Virus ◽

Experimental Infection Model

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Experimental challenge with bovine respiratory syncytial virus in dairy calves: bronchial lymph node transcriptome response

Scientific Reports ◽

10.1038/s41598-019-51094-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Dayle Johnston ◽

Bernadette Earley ◽

Matthew S. McCabe ◽

Ken Lemon ◽

Catherine Duffy ◽

...

Keyword(s):

Gene Expression ◽

Lymph Node ◽

Respiratory Syncytial Virus ◽

Clinical Signs ◽

Bovine Respiratory Syncytial Virus ◽

Holstein Friesian ◽

Differential Gene ◽

Syncytial Virus ◽

Bronchial Lymph Node ◽

And Control

Abstract Bovine Respiratory Disease (BRD) is the leading cause of mortality in calves. The objective of this study was to examine the response of the host’s bronchial lymph node transcriptome to Bovine Respiratory Syncytial Virus (BRSV) in a controlled viral challenge. Holstein-Friesian calves were either inoculated with virus (103.5 TCID50/ml × 15 ml) (n = 12) or mock challenged with phosphate buffered saline (n = 6). Clinical signs were scored daily and blood was collected for haematology counts, until euthanasia at day 7 post-challenge. RNA was extracted and sequenced (75 bp paired-end) from bronchial lymph nodes. Sequence reads were aligned to the UMD3.1 bovine reference genome and differential gene expression analysis was performed using EdgeR. There was a clear separation between BRSV challenged and control calves based on gene expression changes, despite an observed mild clinical manifestation of the disease. Therefore, measuring host gene expression levels may be beneficial for the diagnosis of subclinical BRD. 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. The top enriched pathways included interferon signaling, granzyme B signaling and pathogen pattern recognition receptors, which are responsible for the cytotoxic responses necessary to eliminate the virus.

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Messenger RNA biomarkers of Bovine Respiratory Syncytial Virus infection in the whole blood of dairy calves

Scientific Reports ◽

10.1038/s41598-021-88878-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Dayle Johnston ◽

Bernadette Earley ◽

Matthew S. McCabe ◽

JaeWoo Kim ◽

Jeremy F. Taylor ◽

...

Keyword(s):

Gene Expression ◽

Respiratory Syncytial Virus ◽

Whole Blood ◽

Messenger Rna ◽

Clinical Signs ◽

Bovine Respiratory Syncytial Virus ◽

Dairy Calves ◽

Transcriptomic Response ◽

Syncytial Virus ◽

And Control

AbstractBovine Respiratory Syncytial Virus (BRSV) is a primary viral 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 more accessible in live animals, such as whole blood, they may be used as biomarkers for diagnosis of the disease. Therefore, the objective of the current study was to elucidate the whole blood transcriptomic response of dairy calves to an experimental challenge with BRSV. Calves (Holstein–Friesian) were either administered BRSV inoculate (103.5 TCID50/ml × 15 ml) (n = 12) or 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). The sequence reads were aligned to the bovine reference genome (UMD3.1) and EdgeR was subsequently employed for differential gene expression analysis. Multidimensional scaling showed that samples from BRSV challenged and control calves segregated based on whole blood gene expression changes, despite the BRSV challenged calves only displaying mild clinical symptoms 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 may be beneficial for the diagnosis of subclinical BRD from blood samples.

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