Induction of Atlantic salmon type I interferon and antagonism by infectious pancreatic necrosis virus

• Main Author: Lauksund, Reidunn Silje
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: 2014
• Subjects: VDP::Mathematics and natural science: 400::Basic biosciences: 470::General immunology: 478; VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Generell immunologi: 478; DOKTOR-002; Norway; Bergan; Kileng; Lauksund; Steinsvik; Atlantic salmon
• Online Access: https://hdl.handle.net/10037/6152

The papers of this thesis are not available in Munin: 1. Veronica Bergan, Silje Steinsvik, Hao Xu, Øyvind Kileng and Børre Robertsen: 'Promoters of type I interferon genes from Atlantic salmon contain two main regulatory regions', FEBS Journal (2006), vol. 273:3893–3906. Available at http://dx.doi.org/10.1111/j.1742-4658.2006.05382.x 2. Silje Lauksund, Tina Svingerud, Veronica Bergan and Børre Robertsen: 'Atlantic salmon IPS-1 mediates induction of IFNa1 and activation of NF-kappaB and localizes to mitochondria', Developmental and Comparative Immunology (2009), vol. 33:1196–1204. Available at http://dx.doi.org/10.1016/j.dci.2009.06.012 3. Silje Lauksund, Linn Greiner-Tollersrud and Børre Robertsen: 'Infectious Pancreatic Necrosis Virus Proteins VP2, VP3, VP4 and VP5 Antagonize IFNa1 Promoter Activation while VP1 induces IFNa1' (manuscript). Viral infections are a leading cause of mortality in the farming of Atlantic salmon in Norway. Viral outbreaks cause heavy losses each year, and one of the most predominant viral diseases is infectious pancreatic necrosis (IPN). The virus causing this disease, the infectious pancreatic necrosis virus (IPNV), belongs to the Birnaviridae family of viruses with a double-stranded RNA (dsRNA) genome. Although viral disease is prevalent in the Atlantic salmon aquaculture industry, fish possess an immune system fully equipped to handle viral disease. In this work we have studied induction of the type I interferon (IFN) response in Atlantic salmon in response to intracellular foreign RNA. IFNs are pivotal alarm proteins alerting other cells of the infection, contributing to the establishment of an antiviral state. In order for IFNs to be produced, the cell must recognize the presence of the viral intruder. Viruses are recognized by a wide range of different receptors. The receptors recognize characteristic pathogen associated molecular patterns (PAMPs), for viruses usually the nucleic acids. The receptors proceed to signal through a conserved signaling pathway that culminates in the induction of IFN production. We have identified a central member of the signaling pathway, IPS-1, a signal mediator conserved through evolution. We have also investigated the promoter elements of two type I IFNa promoters, characterizing the regulatory regions. The induction of IFN production is a common target for viral proteins trying to subvert the IFN response and subsequent antiviral state. Using the IFN promoters and IPS-1 protein, we identified IFN antagonistic effects of separate IPNV proteins.