title: Formulations combining CpG containing oliogonucleotides and poly I:C enhance the magnitude of immune responses and protection against pancreas disease in Atlantic salmon.
abstract: Both CpG oligodeoxynucleotides and double-stranded RNA (poly I:C) have documented effects as treatments against several viral diseases in fish. However, as stand-alone treatments their effects have been modest. We have tested here whether CpG and poly I:C, alone or in combination induce protection against Salmonid Alphavirus (SAV), the causative agent of pancreas disease in Atlantic salmon. Our results revealed a significant reduction of viraemia 2 weeks after ip injection of the combined treatment and 1 week after challenge with SAV subtype 3, followed by reduced SAV induced heart pathology 3 weeks later. The SAV titers in blood samples from the combination group were lower as compared to single treatments with either CpG or poly I:C. Surprisingly, reduced SAV levels could also be found in fish as long as 7 weeks after receiving the combination treatment. The expression of IFNγ and to a lesser extent IFNa and Mx was up-regulated in head kidney and spleen 5 days after the fish had been treated with CpG and poly I:C. Furthermore, the complement factor C4 was depleted in serum 8 weeks post treatment, suggesting complement activation leading to C4 consumption. We hypothesize that the CpG/poly I:C-induced protection against SAV3 is mediated by mechanisms involving type I and type II IFN induced antiviral activity and complement mediated protective responses.
authors.affiliation: Norwegian College of Fisheries Science, University of Tromsø, N-9037 Tromsø, Norway.
authors.forename: Guro
authors.initials: G
authors.lastname: Strandskog
authors.forename: Stéphane
authors.initials: S
authors.lastname: Villoing
authors.forename: Dimitar B
authors.initials: DB
authors.lastname: Iliev
authors.forename: Hanna L
authors.initials: HL
authors.lastname: Thim
authors.forename: Karen Elina
authors.initials: KE
authors.lastname: Christie
authors.forename: Jorunn B
authors.initials: JB
authors.lastname: Jørgensen
mesh_terms: D000524:Alphavirus / Q000276:immunology / Q000472:pathogenicity; D018354:Alphavirus Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000276:immunology; D003181:Complement C4 / Q000032:analysis; D015226:Dinucleoside Phosphates; D005393:Fish Diseases / Q000276:immunology* / Q000821:virology; D060226:Head Kidney / Q000187:drug effects / Q000276:immunology; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000276:immunology; D010182:Pancreatic Diseases / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D011070:Poly I-C / Q000008:administration & dosage* / Q000276:immunology; D020317:Salmo salar / Q000276:immunology* / Q000821:virology; D013154:Spleen / Q000187:drug effects / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D003181:Complement C4; D015226:Dinucleoside Phosphates; D007370:Interferon Type I; D007371:Interferon-gamma; D009838:Oligodeoxyribonucleotides; D011070:Poly I-C; C015772:CpG dinucleotide