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dc.contributor.authorWoldemariam, Nardos Tesfaye
dc.contributor.authorAgafonov, Oleg
dc.contributor.authorSindre, Hilde
dc.contributor.authorHøyheim, Bjørn
dc.contributor.authorHouston, Ross D.
dc.contributor.authorRobledo, Diego
dc.contributor.authorBron, James E.
dc.contributor.authorAndreassen, Rune
dc.date.accessioned2020-09-16T06:47:49Z
dc.date.available2020-09-16T06:47:49Z
dc.date.issued2020-09-11
dc.description.abstractInfectious pancreatic necrosis virus (IPNV) infection has been a major problem in salmonid aquaculture. Marker-assisted selection of individuals with resistant genotype at the major IPN quantitative trait locus (IPN-QTL) has significantly reduced mortality in recent years. We have identified host miRNAs that respond to IPNV challenge in salmon fry that were either homozygous resistant (RR) or homozygous susceptible (SS) for the IPN-QTL. Small RNA-sequenced control samples were compared to samples collected at 1, 7, and 20 days post challenge (dpc). This revealed 72 differentially expressed miRNAs (DE miRNAs). Viral load (VL) was lower in RR vs. SS individuals at 7 and 20 dpc. However, analysis of miRNA expression changes revealed no differences between RR vs. SS individuals in controls, at 1 or 7 dpc, while 38 “high viral load responding” miRNAs (HVL-DE miRNAs) were identified at 20 dpc. Most of the HVL-DE miRNAs showed changes that were more pronounced in the high VL SS group than in the low VL RR group when compared to the controls. The absence of differences between QTL groups in controls, 1 and 7 dpc indicates that the QTL genotype does not affect miRNA expression in healthy fish or their first response to viral infections. The miRNA differences at 20 dpc were associated with the QTL genotype and could, possibly, contribute to differences in resistance/susceptibility at the later stage of infection. <i>In silico</i> target gene predictions revealed that 180 immune genes were putative targets, and enrichment analysis indicated that the miRNAs may regulate several major immune system pathways. Among the targets of HVL-DE miRNAs were IRF3, STAT4, NFKB2, MYD88, and IKKA. Interestingly, TNF-alpha paralogs were targeted by different DE miRNAs. Most DE miRNAs were from conserved miRNA families that respond to viral infections in teleost (e.g., miR-21, miR-146, miR-181, miR-192, miR-221, miR-462, miR-731, and miR-8159), while eight were species specific. The miRNAs showed dynamic temporal changes implying they would affect their target genes differently throughout disease progression. This shows that miRNAs are sensitive to VL and disease progression, and may act as fine-tuners of both immediate immune response activation and the later inflammatory processes.en_US
dc.identifier.citationWoldemariam NT, Agafonov O, Sindre H, Høyheim B, Houston RD, Robledo D, Bron JE, Andreassen R. miRNAs Predicted to Regulate Host Anti-viral Gene Pathways in IPNV-Challenged Atlantic Salmon Fry Are Affected by Viral Load, and Associated With the Major IPN Resistance QTL Genotypes in Late Infection. Frontiers in Immunology. 2020;11:2113en_US
dc.identifier.cristinIDFRIDAID 1830183
dc.identifier.doihttps://doi.org/10.3389/fimmu.2020.02113
dc.identifier.issn1664-3224
dc.identifier.urihttps://hdl.handle.net/10037/19391
dc.language.isoengen_US
dc.publisherFrontiers Mediaen_US
dc.relation.journalFrontiers in Immunology
dc.relation.projectIDNorges forskningsråd: 254849en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/HAVBRUK2/254849/Norway/miRNAs and their role in virus disease and immune response in Atlantic salmon//en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Mathematics and natural science: 400::Chemistry: 440en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Kjemi: 440en_US
dc.titlemiRNAs Predicted to Regulate Host Anti-viral Gene Pathways in IPNV-Challenged Atlantic Salmon Fry Are Affected by Viral Load, and Associated With the Major IPN Resistance QTL Genotypes in Late Infectionen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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