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
Infectious 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 mi...
Published in: | Frontiers in Immunology |
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Online Access: | https://hdl.handle.net/10642/9380 https://doi.org/10.3389/fimmu.2020.02113 |
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fthsosloakersoda:oai:oda.oslomet.no:10642/9380 2023-05-15T15:32:21+02:00 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 Woldemariam, Nardos Tesfaye Agafonov, Aleksander Sindre, Hilde Høyheim, Bjørn Andreassen, Rune 2020-09-15T14:27:54Z application/pdf https://hdl.handle.net/10642/9380 https://doi.org/10.3389/fimmu.2020.02113 en eng Frontiers Media Frontiers in Immunology;September 2020 %7C Volume 11 %7C Article 2113 Norges forskningsråd: 254849 Woldemariam NT, Agafonov A, Sindre H, Høyheim B, 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;11:2113 urn:issn:1664-3224 https://hdl.handle.net/10642/9380 https://doi.org/10.3389/fimmu.2020.02113 cristin:1830183 Creative Commons Attribution 4.0 International (CC BY 4.0) License https://creativecommons.org/licenses/by/4.0/ CC-BY Frontiers in Immunology Atlantic salmon Ribonucleic acids MicroRNAs Infectious pancreatic necrosis viruses IPNVs Immune responses Host-virus interactions Journal article Peer reviewed 2020 fthsosloakersoda https://doi.org/10.3389/fimmu.2020.02113 2021-10-11T16:54:52Z Infectious 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. In silico 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. This study was supported by the Research Council of Norway (RCN) grant 254849/E40. publishedVersion Article in Journal/Newspaper Atlantic salmon OsloMet (Oslo Metropolitan University): ODA (Open Digital Archive) Ikka ENVELOPE(-48.100,-48.100,61.150,61.150) Norway Frontiers in Immunology 11 |
institution |
Open Polar |
collection |
OsloMet (Oslo Metropolitan University): ODA (Open Digital Archive) |
op_collection_id |
fthsosloakersoda |
language |
English |
topic |
Atlantic salmon Ribonucleic acids MicroRNAs Infectious pancreatic necrosis viruses IPNVs Immune responses Host-virus interactions |
spellingShingle |
Atlantic salmon Ribonucleic acids MicroRNAs Infectious pancreatic necrosis viruses IPNVs Immune responses Host-virus interactions Woldemariam, Nardos Tesfaye Agafonov, Aleksander Sindre, Hilde Høyheim, Bjørn Andreassen, Rune 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 |
topic_facet |
Atlantic salmon Ribonucleic acids MicroRNAs Infectious pancreatic necrosis viruses IPNVs Immune responses Host-virus interactions |
description |
Infectious 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. In silico 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. This study was supported by the Research Council of Norway (RCN) grant 254849/E40. publishedVersion |
format |
Article in Journal/Newspaper |
author |
Woldemariam, Nardos Tesfaye Agafonov, Aleksander Sindre, Hilde Høyheim, Bjørn Andreassen, Rune |
author_facet |
Woldemariam, Nardos Tesfaye Agafonov, Aleksander Sindre, Hilde Høyheim, Bjørn Andreassen, Rune |
author_sort |
Woldemariam, Nardos Tesfaye |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Frontiers Media |
publishDate |
2020 |
url |
https://hdl.handle.net/10642/9380 https://doi.org/10.3389/fimmu.2020.02113 |
long_lat |
ENVELOPE(-48.100,-48.100,61.150,61.150) |
geographic |
Ikka Norway |
geographic_facet |
Ikka Norway |
genre |
Atlantic salmon |
genre_facet |
Atlantic salmon |
op_source |
Frontiers in Immunology |
op_relation |
Frontiers in Immunology;September 2020 %7C Volume 11 %7C Article 2113 Norges forskningsråd: 254849 Woldemariam NT, Agafonov A, Sindre H, Høyheim B, 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;11:2113 urn:issn:1664-3224 https://hdl.handle.net/10642/9380 https://doi.org/10.3389/fimmu.2020.02113 cristin:1830183 |
op_rights |
Creative Commons Attribution 4.0 International (CC BY 4.0) License https://creativecommons.org/licenses/by/4.0/ |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.3389/fimmu.2020.02113 |
container_title |
Frontiers in Immunology |
container_volume |
11 |
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1766362866936446976 |