title: Infectious hematopoietic necrosis virus (IHNV) persistence in Sockeye Salmon: influence on brain transcriptome and subsequent response to the viral mimic poly(I:C).
abstract: BACKGROUND
  Sockeye Salmon are an iconic species widely distributed throughout the North Pacific. A devastating pathogen of Sockeye Salmon is infectious hematopoietic necrosis virus (IHNV, genus Novirhabdovirus, family Rhabdoviridae). It has been postulated that IHNV is maintained in salmon populations by persisting over the life of its host and/or by residing in natural reservoirs other than its susceptible hosts. Herein we demonstrate the presence of IHNV in the brain of Sockeye Salmon that survived an experimentally-induced outbreak, suggesting the presence of viral persistence in this susceptible species. To understand the viral persistent state in Sockeye Salmon we profiled the transcriptome to evaluate the host response in asymptomatic carriers and to determine what effects (if any) IHNV exposure may have on subsequent virus challenges.
  
  
  RESULTS
  A laboratory disease model to simulate a natural IHNV outbreak in Sockeye Salmon resulted in over a third of the population incurring acute IHN disease and mortality during the first four months after initial exposure. Nine months post IHNV exposure, despite the absence of disease and mortality, a small percentage (<4 %) of the surviving population contained IHNV in brain. Transcriptome analysis in brain of asymptomatic virus carriers and survivors without virus exhibited distinct transcriptional profiles in comparison to naïve fish. Characteristic for carriers was the up-regulation of genes involved in antibody production and antigen presentation. In both carriers and survivors a down-regulation of genes related to cholesterol biosynthesis, resembling an antiviral mechanism observed in higher vertebrates was revealed along with differences in nervous system development. Moreover, following challenge with poly(I:C), survivors and carriers displayed an elevated antiviral immune response in comparison to naïve fish.
  
  
  CONCLUSIONS
  IHN virus persistence was identified in Sockeye Salmon where it elicited a unique brain transcriptome profile suggesting an ongoing adaptive immune response. IHNV carriers remained uncompromised in mounting efficient innate antiviral responses when exposed to a viral mimic. The capacity of IHNV to reside in asymptomatic hosts supports a virus carrier hypothesis and if proven infectious, could have significant epidemiological consequences towards maintaining and spreading IHNV among susceptible host populations.
authors: Fisheries and Oceans Canada, Pacific Biological Station, 3190 Hammond Bay Road, Nanaimo, V9T 6N7, British Columbia, Canada. anita.mueller77@yahoo.de.
authors: Anita
authors: A
authors: Müller
authors: Department of Biology, Centre for Biomedical Research, University of Victoria, Victoria, British Columbia, V8W 3N5, Canada. ben.sutherland.1@ulaval.ca.|Present address: Département de biologie, Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, G1V 0A6, Canada. ben.sutherland.1@ulaval.ca.
authors: Ben J G
authors: BJ
authors: Sutherland
authors: Department of Biology, Centre for Biomedical Research, University of Victoria, Victoria, British Columbia, V8W 3N5, Canada. bkoop@uvic.ca.
authors: Ben F
authors: BF
authors: Koop
authors: Fisheries and Oceans Canada, Pacific Biological Station, 3190 Hammond Bay Road, Nanaimo, V9T 6N7, British Columbia, Canada. Stewart.Johnson@dfo-mpo.gc.ca.
authors: Stewart C
authors: SC
authors: Johnson
authors: Fisheries and Oceans Canada, Pacific Biological Station, 3190 Hammond Bay Road, Nanaimo, V9T 6N7, British Columbia, Canada. Kyle.Garver@dfo-mpo.gc.ca.
authors: Kyle A
authors: KA
authors: Garver
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000821:virology; D002353:Carrier State; D005393:Fish Diseases / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D029142:Infectious hematopoietic necrosis virus / Q000235:genetics / Q000276:immunology; D050356:Lipid Metabolism / Q000235:genetics; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology; D015203:Reproducibility of Results; D012474:Salmon / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D059467:Transcriptome
chemical_list: D011070:Poly I-C