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

2019 ◽  
Vol 9 (1) ◽  
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.

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

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.

scholarly journals Elucidation of the Host Bronchial Lymph Node miRNA Transcriptome Response to Bovine Respiratory Syncytial Virus

2021 ◽  
Vol 12 ◽  
Author(s):  
Dayle Johnston ◽  
Bernadette Earley ◽  
Matthew S. McCabe ◽  
Jaewoo Kim ◽  
Jeremy F. Taylor ◽  
...  
Keyword(s):  
Lymph Node ◽  
Respiratory Syncytial Virus ◽  
Target Genes ◽  
Mirna Gene ◽  
Bovine Respiratory Syncytial Virus ◽  
T Cell Response ◽  
Pathogen Recognition ◽  
Syncytial Virus ◽  
Bronchial Lymph Node ◽  
And Control

Bovine respiratory disease (BRD) causes substantial morbidity and mortality, affecting cattle of all ages. One of the main causes of BRD is an initial inflammatory response to bovine respiratory syncytial virus (BRSV). MicroRNAs are novel and emerging non-coding small RNAs that regulate many biological processes and are implicated in various inflammatory diseases. The objective of the present study was to elucidate the changes in the bovine bronchial lymph node miRNA transcriptome in response to BRSV following an experimental viral challenge. Holstein-Friesian calves were either administered a challenge dose of BRSV (103.5 TCID50/ml × 15 ml) (n = 12) or were mock inoculated with sterile phosphate buffered saline (n = 6). Daily scoring of clinical signs was performed and calves were euthanized at day 7 post-challenge. Bronchial lymph nodes were collected for subsequent RNA extraction and sequencing (75 bp). Read counts for known miRNAs were generated using the miRDeep2 package using the UMD3.1 reference 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. Target genes were examined for enriched pathways and gene ontologies using Ingenuity Pathway Analysis (Qiagen). Multi-dimensional scaling (MDS) based on miRNA gene expression changes, revealed a clearly defined separation between the BRSV challenged and control calves, although the clinical manifestation of disease was only mild. One hundred and nineteen DE miRNAs (P &lt; 0.05, FDR &lt; 0.1, fold change &gt; 1.5) were detected 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. Of the DE predicted target genes, 455 had fold changes that were inverse to the corresponding DE miRNAs. There were eight enriched pathways among the DE predicted target genes with inverse fold changes to their corresponding DE miRNA including: granulocyte and agranulocyte adhesion and diapedesis, interferon signalling 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 of the virus and its subsequent elimination.

scholarly journals Analysis of lung transcriptome in calves infected with Bovine Respiratory Syncytial Virus and treated with antiviral and/or cyclooxygenase inhibitor

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246695
Author(s):  
Maxim Lebedev ◽  
Heather A. McEligot ◽  
Victoria N. Mutua ◽  
Paul Walsh ◽  
Francisco R. Carvallo Chaigneau ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Respiratory Syncytial Virus ◽  
Differential Gene Expression ◽  
Lung Tissue ◽  
Bovine Respiratory Syncytial Virus ◽  
Pathway Enrichment Analysis ◽  
Adaptive Immune ◽  
Differential Gene ◽  
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.

Differential Gene Expression in Young Vs Aged Mice Infected with Respiratory Syncytial Virus

2013 ◽  
Vol 131 (2) ◽  
pp. AB8
Author(s):  
Terianne M. Wong ◽  
Sandhya Boyapalle ◽  
Siddarth Kamath ◽  
Huy Nguyen ◽  
Subhra Mohapatra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Respiratory Syncytial Virus ◽  
Differential Gene Expression ◽  
Aged Mice ◽  
Differential Gene ◽  
Syncytial Virus

scholarly journals Supplementing a Saccharomyces cerevisiae fermentation product modulates innate immune function and ameliorates bovine respiratory syncytial virus infection in neonatal calves

2020 ◽  
Vol 98 (8) ◽  
Author(s):  
Asmaa H A Mahmoud ◽  
Jamison R Slate ◽  
Suyeon Hong ◽  
Ilkyu Yoon ◽  
Jodi L McGill
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Respiratory Syncytial Virus ◽  
Immune Function ◽  
Clinical Signs ◽  
Bovine Respiratory Syncytial Virus ◽  
Dairy Calves ◽  
Lung Pathology ◽  
Fermentation Products ◽  
Supplementation Period ◽  
Syncytial Virus

Abstract The objectives of this study were to determine the effects of oral supplementation with Saccharomyces cerevisiae fermentation products (SCFP; SmartCare and NutriTek; Diamond V, Cedar Rapids, IA) on immune function and bovine respiratory syncytial virus (BRSV) infection in preweaned dairy calves. Twenty-four Holstein × Angus, 1- to 2-d-old calves (38.46 ± 0.91 kg initial body weight [BW]) were assigned two treatment groups: control or SCFP treated, milk replacer with 1 g/d SCFP (SmartCare) and calf starter top-dressed with 5 g/d SCFP (NutriTek). The study consisted of one 31-d period. On days 19 to 21 of the supplementation period, calves were challenged via aerosol inoculation with BRSV strain 375. Calves were monitored twice daily for clinical signs, including rectal temperature, cough, nasal and ocular discharge, respiration effort, and lung auscultation. Calves were euthanized on day 10 postinfection (days 29 to 31 of the supplementation period) to evaluate gross lung pathology and pathogen load. Supplementation with SCFP did not affect BW (P = 0.762) or average daily gain (P = 0.750), percentages of circulating white blood cells (P &lt; 0.05), phagocytic (P = 0.427 for neutrophils and P = 0.460 for monocytes) or respiratory burst (P = 0.119 for neutrophils and P = 0.414 for monocytes) activity by circulating leukocytes either before or following BRSV infection, or serum cortisol concentrations (P = 0.321) after BRSV infection. Calves receiving SCFP had reduced clinical disease scores compared with control calves (P = 0.030), reduced airway neutrophil recruitment (P &lt; 0.002), reduced lung pathology (P = 0.031), and a reduced incidence of secondary bacterial infection. Calves receiving SCFP shed reduced virus compared with control calves (P = 0.049) and tended toward lower viral loads in the lungs (P = 0.051). Immune cells from the peripheral blood of SCFP-treated calves produced increased (P &lt; 0.05) quantities of interleukin (IL)-6 and tumor necrosis factor-alpha in response to toll-like receptor stimulation, while cells from the bronchoalveolar lavage (BAL) of SCFP-treated calves secreted less (P &lt; 0.05) proinflammatory cytokines in response to the same stimuli. Treatment with SCFP had no effect on virus-specific T cell responses in the blood but resulted in reduced (P = 0.045) virus-specific IL-17 secretion by T cells in the BAL. Supplementing with SCFP modulates both systemic and mucosal immune responses and may improve the outcome of an acute respiratory viral infection in preweaned dairy calves.

Experimental Bovine Respiratory Tract Disease with Haemophilus somnus

1988 ◽  
Vol 25 (2) ◽  
pp. 124-130 ◽  
Author(s):  
L. N. D. Potgieter ◽  
R. G. Helman ◽  
W. Greene ◽  
M. A. Breider ◽  
E. T. Thurber ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Disease Control ◽  
Clinical Signs ◽  
Bovine Respiratory Syncytial Virus ◽  
Respiratory Tract Disease ◽  
Naturally Occurring ◽  
Haemophilus Somnus ◽  
Syncytial Virus ◽  
Tract Disease

Eight calves were inoculated into the bronchus with H. somnus. Thirteen calves were inoculated with bovine respiratory syncytial virus (BRSV) and 8 days later with H. somnus. All calves developed necrotizing, suppurative, lobular bronchopneumonia and pleuritis. Clinical signs of disease and pneumonic lesions were significantly more severe in calves that were sequentially inoculated with BRSV followed by H. somnus. Pneumonic lesions in the inoculated calves were similar to those described for naturally occurring H. somnus-associated respiratory tract disease. Control calves inoculated with BRSV alone or sham-inoculated with medium did not develop clinical signs of respiratory tract disease. The BRSV-inoculated control calves developed minimal pneumonic lesions.

scholarly journals Bovine Respiratory Syncytial Virus (BRSV) Infection Detected in Exhaled Breath Condensate of Dairy Calves by Near-Infrared Aquaphotomics

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 549
Author(s):  
Mariana Santos-Rivera ◽  
Amelia R. Woolums ◽  
Merrilee Thoresen ◽  
Florencia Meyer ◽  
Carrie K. Vance
Keyword(s):  
Respiratory Syncytial Virus ◽  
Near Infrared ◽  
Exhaled Breath Condensate ◽  
Clinical Signs ◽  
Rapid Identification ◽  
Bovine Respiratory Syncytial Virus ◽  
Dairy Calves ◽  
Exhaled Breath ◽  
Syncytial Virus ◽  
Breath Condensate

Bovine respiratory syncytial virus (BRSV) is a major contributor to respiratory disease in cattle worldwide. Traditionally, BRSV infection is detected based on non-specific clinical signs, followed by reverse transcriptase-polymerase chain reaction (RT-PCR), the results of which can take days to obtain. Near-infrared aquaphotomics evaluation based on biochemical information from biofluids has the potential to support the rapid identification of BRSV infection in the field. This study evaluated NIR spectra (n = 240) of exhaled breath condensate (EBC) from dairy calves (n = 5) undergoing a controlled infection with BRSV. Changes in the organization of the aqueous phase of EBC during the baseline (pre-infection) and infected (post-infection and clinically abnormal) stages were found in the WAMACS (water matrix coordinates) C1, C5, C9, and C11, likely associated with volatile and non-volatile compounds in EBC. The discrimination of these chemical profiles by PCA-LDA models differentiated samples collected during the baseline and infected stages with an accuracy, sensitivity, and specificity >93% in both the calibration and validation. Thus, biochemical changes occurring during BRSV infection can be detected and evaluated with NIR-aquaphotomics in EBC. These findings form the foundation for developing an innovative, non-invasive, and in-field diagnostic tool to identify BRSV infection in cattle.

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