Subgrouping of bovine respiratory syncytial virus strains detected in lung tissue

Bovine respiratory syncytial virus (BRSV) is able to counteract the alpha/beta interferon (IFN-α/β)-mediated antiviral response for efficient replication in a host-specific manner. Mice models have been developed for experimental infection with human, but not bovine, respiratory syncytial virus strains. Here, it is shown that BRSV can replicate efficiently on primary cell cultures derived from type I IFN receptor-deficient, but not from wild-type IFN-competent, mice. However, BRSV infection was not enhanced in mice devoid of the type I IFN receptor. These results show that type I IFN is a major host-range determinant for infection at the cellular level, but that other factors control virus replication and pathology in vivo.

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

PLoS ONE ◽

10.1371/journal.pone.0246695 ◽

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.

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Circulation of Indigenous Bovine Respiratory Syncytial Virus Strains in Turkish Cattle: The First Isolation and Molecular Characterization

Animals ◽

10.3390/ani10091700 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1700

Author(s):

Zafer Yazici ◽

Emre Ozan ◽

Cuneyt Tamer ◽

Bahadir Muftuoglu ◽

Gerald Barry ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Molecular Characterization ◽

Beef Cows ◽

Bovine Respiratory Syncytial Virus ◽

Molecular Characteristics ◽

Specific Primers ◽

Antigen Elisa ◽

Syncytial Virus ◽

Virus Strains

Bovine respiratory disease (BRD) is a huge economic burden on the livestock industries of countries worldwide. Bovine respiratory syncytial virus (BRSV) is one of the most important pathogens that contributes to BRD. In this study, we report the identification and first isolation, with molecular characterization, of a new BRSV strain from lung specimens of three beef cows in Turkey that died from respiratory distress. After the screening of lung tissues for BRD-associated viruses using a multiscreen antigen-ELISA, a BRSV antigen was detected. This was then confirmed by real-time RT-PCR specific for BRSV. Following confirmation, virus isolation was conducted in MDBK cell cultures and clear CPE, including syncytia compatible with BRSV, were detected. RT-nested PCR, using F gene-specific primers, was performed on the cultured isolates, and the products were sequenced and deposited to Genbank with accession numbers MT179304, MT024766, and MT0244767. Phylogenetic analysis of these sequences indicated that the cattle were infected with BRSV from subgroup III and were closely related to previously identified American and Turkish strains, but contained some amino acid and nucleotide differences. This research paves the way for further studies on the molecular characteristics of natural BRSV isolates, including full genome analysis and disease pathogenesis, and also contributes to the development of robust national strategies against this virus.

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Infected Cell Types in Ovine Lung Following Exposure to Bovine Respiratory Syncytial Virus

Veterinary Pathology ◽

10.1177/030098589403100210 ◽

1994 ◽

Vol 31 (2) ◽

pp. 229-236 ◽

Cited By ~ 13

Author(s):

J. T. Meehan ◽

R. C. Cutlip ◽

H. D. Lehmkuhl ◽

J. P. Kluge ◽

M. R. Ackermann

Keyword(s):

Respiratory Syncytial Virus ◽

Lymph Nodes ◽

Lung Tissue ◽

Viral Antigen ◽

Bovine Respiratory Syncytial Virus ◽

Post Inoculation ◽

Type I ◽

Mediastinal Lymph Nodes ◽

Bronchiolar Epithelium ◽

Syncytial Virus

Sixteen adult sheep (ten females, six males obtained from a closed flock at National Animal Disease Center, Ames, IA) were experimentally infected with bovine respiratory syncytial virus strain 375 (BRSV), and lung tissues were stained for viral antigen. Two infected sheep were euthanatized at each of the following post-inoculation times: 12, 24, 36, 48, 72, 96, 144, and 192 hours. Lung, nasal turbinates, trachea, right cranial bronchial and mediastinal lymph nodes, liver, and spleen were collected for histologic evaluation. An indirect immunoperoxidase technique was performed on routine paraffin-embedded sections of lung tissue, trachea, turbinates, and bronchial and mediastinal lymph nodes to determine the location of the BRSV antigen. For lung tissue from each sheep 400 light microscopic fields at 160x magnification were examined for staining for BRSV antigen. Lung tissue was also collected for virus and bacterial isolation. Daily serum samples were taken for determination of anti-BRSV titers. Severe respiratory disease was not produced in any sheep. Bovine respiratory syncytial virus was isolated from lung tissue collected from all sheep up through 144 hours postinoculation. At 12 hours post-inoculation (case No. 2) respiratory syncytial virus antigen was detected in bronchiolar epithelium and a mononuclear cell within an alveolar space. Lung tissue from the sheep necropsied between 24 and 144 hours postinoculattion (case Nos. 3–14) contained BRSV antigen in bronchiolar epithelium, type I pneumocytes, type II pneumocytes. alveolar macrophages, and mononuclear cells within alveolar spaces. Macrophages staining for viral antigen were rare. Bronchiolar and type I epithelial cells comprised the majority of infected cells. In a separate experiment, lung slices inoculated in vitro with either BRSV or ovine adenovirus did not stain for the respective antigens. Slices inoculated with parainfluenzavirus-3 did stain for that viral antigen.

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