Trial lecture title: Viral interference with host immune defence.
Ordinary opponents
- First opponent: Professor Niels Lorenzen, National Institute of Aquatic Resources Technical University of Denmark
- Second opponent: Hetron Mweemba Munang'andu, PhD, Faculty of Veterinary Medicine and Biosciences Section of Aquatic Medicine and Nutrition, Norwegian University of Life Sciences
- Leader of the Committee: Associate Professor Hege Smith Tunsjø, Department of Life Sciences and Health, Faculty of Health Sciences, OsloMet
Leader of the public defense is Associate Professor Ole Herman Ambur, Department of Life Sciences and Health, Faculty of Health Sciences, OsloMet.
The main supervisor is Professer Rune Andreassen, Department of Life Sciences and Health, Faculty of Health Sciences, OsloMet.
The co-supervisors are Bjørn Høyheim, Researcher, Faculty of Veterinary Medicine, NMBU and Hilde Sindre, Fish Health Research, the Norwegian Veterinary Institute.
Thesis abstract
Viral diseases are one of the main challenges for the Norwegian Atlantic salmon farming industry. MicroRNAs (miRNAs) are key post-transcriptional regulators of immune homeostasis, suggested as biomarkers and, potentially, molecular means to combat diseases.
At the initiation of this project, a few studies in fish had indicated the potential involvement of host miRNAs in regulating the immune response to viral infections. However, the role of miRNAs in viral diseases and immune responses in Atlantic salmon were previously uncharacterized. The work presented in this thesis set out to identify Atlantic salmon miRNAs responding to viral infections caused by the salmonid alphavirus (SAV) and infectious pancreatic necrosis virus (IPNV).
Utilizing high-throughput sequencing and bioinformatic approaches, we performed miRNA characterization in different organs, developmental stages, and disease conditions, as well as the first characterization of isomiRs in Atlantic salmon, which resulted in the discovery of about a hundred new miRNA genes. The resulting miRNAome serves as the reference for HTS-based expression studies to understand the miRNA mediated gene regulation in this species.
Two studies
The two challenge studies identified 85 conserved and eight species-specific miRNAs from 50 miRNA families that changed expression (DE miRNAs) in response to viral infections (SAV and IPNV). Furthermore, there were differences in responses associated with virus genotypes causing moderate or high mortality (SAV) or host genetics (susceptibility to disease (IPNV).
The miRNA expression changes were dynamic in a time-dependent manner post-infection. Eight mature miRNAs from four miRNA families (miR-21, miR-146, miR-462, and miR-731) were common for SAV and IPNV infections. This small group of conserved miRNAs has been shown to respond to viral infections in several species, further indicating their involvement in regulating the immune response.
In-silico predictions, gene ontology (GO), and pathway analysis revealed that several of the miRNA target genes were enriched in immune signaling pathways, suggesting a role for the DE miRNAs in the context of the antiviral immune response, perhaps through coordinated effects on several immune-system pathways.
Results
Ultimately, based on the stage of infection and function of their target genes, our results suggest that miRNAs may help fine-tune both the activation of the early antiviral immune response and control the long-term, possibly pathological, inflammatory responses.
While the miRNA-target gene interactions revealed in our studies need to be explored in functional assays to define the individual roles of the miRNAs, the DE miRNAs may also be further explored as biomarkers of infection or inflammation.
