title: Epithelial Cadherin Determines Resistance to Infectious Pancreatic Necrosis Virus in Atlantic Salmon.
abstract: Infectious pancreatic necrosis virus (IPNV) is the cause of one of the most prevalent diseases in farmed Atlantic salmon (Salmo salar). A quantitative trait locus (QTL) has been found to be responsible for most of the genetic variation in resistance to the virus. Here we describe how a linkage disequilibrium-based test for deducing the QTL allele was developed, and how it was used to produce IPN-resistant salmon, leading to a 75% decrease in the number of IPN outbreaks in the salmon farming industry. Furthermore, we describe how whole-genome sequencing of individuals with deduced QTL genotypes was used to map the QTL down to a region containing an epithelial cadherin (cdh1) gene. In a coimmunoprecipitation assay, the Cdh1 protein was found to bind to IPNV virions, strongly indicating that the protein is part of the machinery used by the virus for internalization. Immunofluorescence revealed that the virus colocalizes with IPNV in the endosomes of homozygous susceptible individuals but not in the endosomes of homozygous resistant individuals. A putative causal single nucleotide polymorphism was found within the full-length cdh1 gene, in phase with the QTL in all observed haplotypes except one; the absence of a single, all-explaining DNA polymorphism indicates that an additional causative polymorphism may contribute to the observed QTL genotype patterns. Cdh1 has earlier been shown to be necessary for the internalization of certain bacteria and fungi, but this is the first time the protein is implicated in internalization of a virus.
authors.affiliation: AquaGen, 7462 Trondheim, Norway thomas.moen@aquagen.no.
authors.forename: Thomas
authors.initials: T
authors.lastname: Moen
authors.affiliation: AquaGen, 7462 Trondheim, Norway.
authors.forename: Jacob
authors.initials: J
authors.lastname: Torgersen
authors.affiliation: AquaGen, 7462 Trondheim, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Santi
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6 Canada.
authors.forename: William S
authors.initials: WS
authors.lastname: Davidson
authors.affiliation: Nofima, NO-9291 Tromsø, Norway.
authors.forename: Matthew
authors.initials: M
authors.lastname: Baranski
authors.affiliation: AquaGen, 7462 Trondheim, Norway.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Ødegård
authors.affiliation: AquaGen, 7462 Trondheim, Norway.
authors.forename: Sissel
authors.initials: S
authors.lastname: Kjøglum
authors.affiliation: Centre for Integrative Genetics and Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, 1432 Ås, Norway.
authors.forename: Bente
authors.initials: B
authors.lastname: Velle
authors.affiliation: Centre for Integrative Genetics and Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, 1432 Ås, Norway.
authors.forename: Matthew
authors.initials: M
authors.lastname: Kent
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6 Canada.
authors.forename: Krzysztof P
authors.initials: KP
authors.lastname: Lubieniecki
authors.affiliation: Vaxxinova, 5006 Bergen, Norway.
authors.forename: Eivind
authors.initials: E
authors.lastname: Isdal
authors.affiliation: Centre for Integrative Genetics and Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, 1432 Ås, Norway.
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Lien
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017756:Aquaculture; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002874:Chromosome Mapping; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D054884:Host-Pathogen Interactions; D018061:Infectious pancreatic necrosis virus / Q000502:physiology*; D015810:Linkage Disequilibrium / Q000235:genetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics; D020317:Salmo salar / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000821:virology*; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D015820:Cadherins; D005819:Genetic Markers
keywords: IPN; QTL; cadherin; disease resistance; salmon