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      Comparative Genomics Identifies Candidate Genes for Infectious Salmon Anemia (ISA) Resistance in Atlantic Salmon ( Salmo salar)

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          Abstract

          Infectious salmon anemia (ISA) has been described as the hoof and mouth disease of salmon farming. ISA is caused by a lethal and highly communicable virus, which can have a major impact on salmon aquaculture, as demonstrated by an outbreak in Chile in 2007. A quantitative trait locus (QTL) for ISA resistance has been mapped to three microsatellite markers on linkage group (LG) 8 (Chr 15) on the Atlantic salmon genetic map. We identified bacterial artificial chromosome (BAC) clones and three fingerprint contigs from the Atlantic salmon physical map that contains these markers. We made use of the extensive BAC end sequence database to extend these contigs by chromosome walking and identified additional two markers in this region. The BAC end sequences were used to search for conserved synteny between this segment of LG8 and the fish genomes that have been sequenced. An examination of the genes in the syntenic segments of the tetraodon and medaka genomes identified candidates for association with ISA resistance in Atlantic salmon based on differential expression profiles from ISA challenges or on the putative biological functions of the proteins they encode. One gene in particular, HIV-EP2/MBP-2, caught our attention as it may influence the expression of several genes that have been implicated in the response to infection by infectious salmon anemia virus (ISAV). Therefore, we suggest that HIV-EP2/MBP-2 is a very strong candidate for the gene associated with the ISAV resistance QTL in Atlantic salmon and is worthy of further study.

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          The online version of this article (doi:10.1007/s10126-010-9284-0) contains supplementary material, which is available to authorized users.

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          Most cited references47

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          Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA.

          Interferons (IFNs) are critical for protection from viral infection, but the pathways linking virus recognition to IFN induction remain poorly understood. Plasmacytoid dendritic cells produce vast amounts of IFN-alpha in response to the wild-type influenza virus. Here, we show that this requires endosomal recognition of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce TLR7-dependent production of inflammatory cytokines. These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.
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            Interferon-induced Mx proteins in antiviral host defense.

            Mx proteins are key components of the antiviral state induced by interferons in many species. They belong to the class of dynamin-like large guanosine triphosphatases (GTPases) known to be involved in intracellular vesicle trafficking and organelle homeostasis. Mx GTPases share structural and functional properties with dynamin, such as self-assembly and association with intracellular membranes. A unique property of some Mx GTPases is their antiviral activity against a wide range of RNA viruses, including influenza viruses and members of the bunyavirus family. These viruses are inhibited at an early stage in their life cycle, soon after host cell entry and before genome amplification. The mouse Mx1 GTPase accumulates in the cell nucleus where it associates with components of the PML nuclear bodies and inhibits influenza and Thogoto viruses known to replicate in the nucleus. The human MxA GTPase accumulates in the cytoplasm and is partly associated with a COP-I-positive subcompartment of the endoplasmic reticulum. This membrane compartment seems to provide an interaction platform that facilitates viral target recognition. In the case of bunyaviruses, MxA recognizes the viral nucleocapsid protein and interferes with its role in viral genome replication. In the case of Thogoto virus, MxA recognizes the viral nucleoprotein and prevents the incoming viral nucleocapsids from being transported into the nucleus, the site of viral transcription and replication. In both cases, GTP-binding and carboxy-terminal effector functions of MxA are required for target recognition. In general, Mx GTPases appear to detect viral infection by sensing nucleocapsid-like structures. As a consequence, these viral components are trapped and sorted to locations where they become unavailable for the generation of new virus particles.
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              Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections

              The genetic make-up of the host has a major influence on its response to combat pathogens. For influenza A virus, several single gene mutations have been described which contribute to survival, the immune response and clearance of the pathogen by the host organism. Here, we have studied the influence of the genetic background to influenza A H1N1 (PR8) and H7N7 (SC35M) viruses. The seven inbred laboratory strains of mice analyzed exhibited different weight loss kinetics and survival rates after infection with PR8. Two strains in particular, DBA/2J and A/J, showed very high susceptibility to viral infections compared to all other strains. The LD50 to the influenza virus PR8 in DBA/2J mice was more than 1000-fold lower than in C57BL/6J mice. High susceptibility in DBA/2J mice was also observed after infection with influenza strain SC35M. In addition, infected DBA/2J mice showed a higher viral load in their lungs, elevated expression of cytokines and chemokines, and a more severe and extended lung pathology compared to infected C57BL/6J mice. These findings indicate a major contribution of the genetic background of the host to influenza A virus infections. The overall response in highly susceptible DBA/2J mice resembled the pathology described for infections with the highly virulent influenza H1N1-1918 and newly emerged H5N1 viruses.
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                Author and article information

                Contributors
                +1-778-7825637 , +1-778-7825583 , wdavidso@sfu.ca
                Journal
                Mar Biotechnol (NY)
                Marine Biotechnology (New York, N.y.)
                Springer-Verlag (New York )
                1436-2228
                1436-2236
                16 April 2010
                16 April 2010
                April 2011
                : 13
                : 2
                : 232-241
                Affiliations
                [1 ]Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC Canada V5A 1S6
                [2 ]Department of Biology, University of Victoria, Victoria, BC Canada V8W 3N5
                Article
                9284
                10.1007/s10126-010-9284-0
                3084937
                20396924
                3c3c51ef-f2f6-44c7-93f8-2dff9f1b027f
                © The Author(s) 2010
                History
                : 19 December 2009
                : 4 March 2010
                Categories
                Original Article
                Custom metadata
                © Springer Science+Business Media, LLC 2011

                Biotechnology
                atlantic salmon,disease resistance,comparative genomics,infectious salmon anemia
                Biotechnology
                atlantic salmon, disease resistance, comparative genomics, infectious salmon anemia

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