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

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dc.contributor.authorLebedev, Maximen
dc.contributor.authorMcEligot, Heather A.en
dc.contributor.authorMutua, Victoria N.en
dc.contributor.authorWalsh, Paulen
dc.contributor.authorCarvallo, Francisco R.en
dc.contributor.authorGershwin, Laurel J.en
dc.date.accessioned2021-05-17T19:43:05Zen
dc.date.available2021-05-17T19:43:05Zen
dc.date.issued2021-02-18en
dc.description.abstractBovine 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.en
dc.description.notesThis work was funded by USDA NIFA (dual purpose/dual benefit) grant #2017-6701526083 awarded to LJG and PW (http://www.nifa.usda.gov) and UC Davis Comparative Medical Science Training Program (NIH Grant #T32 OD011147) awarded to Nicole Baumgarth, which funded trainee VNM (https://www.nih.gov).The DNA Technologies and Expression Analysis Cores at the UC Davis Genome Center are supported by a NIH shared Instrumentation Grant 1S10OD010786-01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.description.sponsorshipUSDA NIFAUnited States Department of Agriculture (USDA) [2017-6701526083]; UC Davis Comparative Medical Science Training Program (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [T32 OD011147]; NIH shared Instrumentation GrantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1S10OD010786-01]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0246695en
dc.identifier.issn1932-6203en
dc.identifier.issue2en
dc.identifier.othere0246695en
dc.identifier.pmid33600498en
dc.identifier.urihttp://hdl.handle.net/10919/103343en
dc.identifier.volume16en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleAnalysis of lung transcriptome in calves infected with Bovine Respiratory Syncytial Virus and treated with antiviral and/or cyclooxygenase inhibitoren
dc.title.serialPLOS Oneen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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