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      Infectious hematopoietic necrosis virus (IHNV) persistence in Sockeye Salmon: influence on brain transcriptome and subsequent response to the viral mimic poly(I:C)

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          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.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12864-015-1759-y) contains supplementary material, which is available to authorized users.

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          Most cited references96

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          Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation.

          Y. H. Yang (2002)
          There are many sources of systematic variation in cDNA microarray experiments which affect the measured gene expression levels (e.g. differences in labeling efficiency between the two fluorescent dyes). The term normalization refers to the process of removing such variation. A constant adjustment is often used to force the distribution of the intensity log ratios to have a median of zero for each slide. However, such global normalization approaches are not adequate in situations where dye biases can depend on spot overall intensity and/or spatial location within the array. This article proposes normalization methods that are based on robust local regression and account for intensity and spatial dependence in dye biases for different types of cDNA microarray experiments. The selection of appropriate controls for normalization is discussed and a novel set of controls (microarray sample pool, MSP) is introduced to aid in intensity-dependent normalization. Lastly, to allow for comparisons of expression levels across slides, a robust method based on maximum likelihood estimation is proposed to adjust for scale differences among slides.
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            Regulation of MHC class II gene expression by the class II transactivator.

            MHC class II molecules are pivotal for the adaptive immune system, because they guide the development and activation of CD4+ T helper cells. Fulfilling these functions requires that the genes encoding MHC class II molecules are transcribed according to a strict cell-type-specific and quantitatively modulated pattern. This complex gene-expression profile is controlled almost exclusively by a single master regulatory factor, which is known as the class II transactivator. As we discuss here, differential activation of the three independent promoters that drive expression of the gene encoding the class II transactivator ultimately determines the exquisitely regulated pattern of MHC class II gene expression.
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              Immune surveillance in the central nervous system

              Despite being protected by the blood-brain barrier, the CNS must constantly be monitored for insult or pathogen invasion. In this review, the authors illustrate the molecular and cellular players that preside over this surveillance of the brain and spinal cord.
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                Author and article information

                Contributors
                anita.mueller77@yahoo.de
                ben.sutherland.1@ulaval.ca
                bkoop@uvic.ca
                Stewart.Johnson@dfo-mpo.gc.ca
                Kyle.Garver@dfo-mpo.gc.ca
                Journal
                BMC Genomics
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                26 August 2015
                26 August 2015
                2015
                : 16
                : 1
                : 634
                Affiliations
                [ ]Fisheries and Oceans Canada, Pacific Biological Station, 3190 Hammond Bay Road, Nanaimo, V9T 6N7 British Columbia, Canada
                [ ]Department of Biology, Centre for Biomedical Research, University of Victoria, Victoria, British Columbia, V8W 3N5 Canada
                [ ]Present address: Département de biologie, Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, G1V 0A6 Canada
                Article
                1759
                10.1186/s12864-015-1759-y
                4549833
                26306576
                5cb3a798-549c-48ba-86b8-a016af3cbc4a
                © Müller et al. 2015

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 4 March 2015
                : 7 July 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Genetics
                sockeye salmon,infectious hematopoietic necrosis virus (ihnv),brain,ihnv persistence,poly(i:c) injection,immune response,transcriptomics

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