{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:04:46Z","timestamp":1790075086089,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Fish Diseases"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Infectious salmon anaemia (ISA) affects Atlantic salmon (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Salmo salar<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) and is caused by the ISA virus (ISAV). The disease is associated with ISAV strains with deletions in the hemagglutinin\u2010esterase protein, named HPR\u0394 variants. The present study was initially designed as a vaccine efficacy study against ISA. Considerable variability in mortality in virus\u2010injected fish was observed in repeated experimental challenges using the NO\/Finnmark\/NVI\u201070\u201072\/2020 isolate. Four independent experimental challenge trials were conducted. In two experiments, high cumulative mortality was seen in intraperitoneally (i.p.) injected fish. In contrast, considerably lower cumulative mortality was observed in i.p. injected fish in two other experiments. Mortality among cohabitant fish was moderate in one experiment and low or absent in two others. The observed inconsistency precluded reliable assessment of vaccine efficacy and implied investigation into factors underlying the outcome reproducibility between the experimental challenges. To investigate the observed variation in outcomes, fish, virus, and physical conditions were compared in detail. One notable difference among the challenge experiments was tank volume. Mortality was higher among fish injected with virus in smaller tanks than in larger ones. Further examination of the physical and biological variables failed to identify any other definitive determining factors. In addition, to investigate whether the comparatively delayed mortality induced by the injected NO\/Finnmark\/NVI\u201070\u201072\/2020 isolate was associated with early virus\u2013host interactions, a time\u2010course study was conducted to quantify relative viral RNA levels and innate immune responses in ASK\u2010II cells. A highly virulent isolate induced greater expression of innate immune response genes, which may be attributable to the higher amount of viral RNA present in the inoculum despite comparable levels of infectious virus. Collectively, these findings suggest that subtle differences in experimental conditions may contribute to variation in disease outcome and indicate that further research is required to improve understanding of fundamental ISAV biological characteristics.\n                  <\/jats:p>","DOI":"10.1111\/jfd.70291","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:25:41Z","timestamp":1790072741000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Variable Infection Outcomes in Repeated Experimental Challenges of Atlantic Salmon (\n                    <i>Salmo salar<\/i>\n                    ) With an Infectious Salmon Anaemia Virus Isolate"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1221-6182","authenticated-orcid":false,"given":"Lars Ole Sti","family":"Dahl","sequence":"first","affiliation":[{"name":"Faculty of Veterinary Medicine Norwegian University of Life Sciences  \u00c5s Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine","family":"Braaen","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine Norwegian University of Life Sciences  \u00c5s Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0811-7305","authenticated-orcid":false,"given":"\u00d8ystein","family":"Wessel","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine Norwegian University of Life Sciences  \u00c5s Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5837-5006","authenticated-orcid":false,"given":"Johanna Hol","family":"Fosse","sequence":"additional","affiliation":[{"name":"Norwegian Veterinary Institute  \u00c5s Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9911-5948","authenticated-orcid":false,"given":"Espen","family":"Rimstad","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine Norwegian University of Life Sciences  \u00c5s Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"issue":"4","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/jfd.12225","article-title":"Infectious Salmon Anaemia \u2010 Pathogenesis and Tropism","volume":"37","author":"Aamelfot M.","year":"2014","journal-title":"Journal of Fish Diseases"},{"issue":"19","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"10571","DOI":"10.1128\/JVI.00047-12","article-title":"Expression of the Infectious Salmon Anemia Virus Receptor on Atlantic Salmon Endothelial Cells Correlates With the Cell Tropism of the Virus","volume":"86","author":"Aamelfot M.","year":"2012","journal-title":"Journal of Virology"},{"issue":"6","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1099\/0022-1317-76-6-1353","article-title":"Isolation of the Causal Virus of Infectious Salmon Anaemia (ISA) in a Long\u2010Term Cell Line From Atlantic Salmon Head Kidney","volume":"76","author":"Dannevig B. H.","year":"1995","journal-title":"Journal of General Virology"},{"issue":"7","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1099\/vir.0.81687-0","article-title":"Sequence Analysis of the Fusion Protein Gene From Infectious Salmon Anemia Virus Isolates: Evidence of Recombination and Reassortment","volume":"87","author":"Devold M.","year":"2006","journal-title":"Journal of General Virology"},{"issue":"1","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3354\/dao040009","article-title":"Use of RT\u2010PCR for Diagnosis of Infectious Salmon Anaemia Virus (ISAV) in Carrier Sea Trout \n                     Salmo trutta\n                   After Experimental Infection","volume":"40","author":"Devold M.","year":"2000","journal-title":"Diseases of Aquatic Organisms"},{"issue":"2","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3354\/dao034077","article-title":"Characterization and Applications of a Monoclonal Antibody Against Infectious Salmon Anaemia Virus","volume":"34","author":"Falk K.","year":"1998","journal-title":"Diseases of Aquatic Organisms"},{"issue":"12","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"9016","DOI":"10.1128\/jvi.71.12.9016-9023.1997","article-title":"Characterization of Infectious Salmon Anemia Virus, an Orthomyxo\u2010Like Virus Isolated From Atlantic Salmon (\n                     Salmo salar\n                   L.)","volume":"71","author":"Falk K.","year":"1997","journal-title":"Journal of Virology"},{"issue":"10","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"e0142020","DOI":"10.1371\/journal.pone.0142020","article-title":"Dual Mutation Events in the Haemagglutinin\u2010Esterase and Fusion Protein From an Infectious Salmon Anaemia Virus HPR0 Genotype Promote Viral Fusion and Activation by an Ubiquitous Host Protease","volume":"10","author":"Fourrier M.","year":"2015","journal-title":"PLoS One"},{"issue":"1","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1186\/s12864-021-07671-6","article-title":"Exploring Genetic Resistance to Infectious Salmon Anaemia Virus in Atlantic Salmon by Genome\u2010Wide Association and RNA Sequencing","volume":"22","author":"Gervais O.","year":"2021","journal-title":"BMC Genomics"},{"issue":"1","key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.aquaculture.2005.10.041","article-title":"Size\u2010Dependent Susceptibility to Infectious Salmon Anemia Virus (ISAV) in Atlantic Salmon (\n                     Salmo salar\n                   L.) of Farm, Hybrid and Wild Parentage","volume":"254","author":"Glover K. 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With Different Infectious Salmon Anaemia Virus Isolates","volume":"150","author":"Mjaaland S.","year":"2005","journal-title":"Archives of Virology"},{"issue":"10","key":"e_1_2_11_29_1","doi-asserted-by":"crossref","first-page":"7681","DOI":"10.1128\/jvi.71.10.7681-7686.1997","article-title":"Genomic Characterization of the Virus Causing Infectious Salmon Anemia in Atlantic Salmon (\n                     Salmo salar\n                   L.): An Orthomyxo\u2010Like Virus in a Teleost","volume":"71","author":"Mjaaland S.","year":"1997","journal-title":"Journal of Virology"},{"key":"e_1_2_11_30_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1471-2156-8-53","article-title":"Mapping of a Quantitative Trait Locus for Resistance Against Infectious Salmon Anaemia in Atlantic Salmon (\n                     Salmo salar\n                  ): Comparing Survival Analysis With Analysis on Affected\/Resistant Data","volume":"8","author":"Moen T.","year":"2007","journal-title":"BMC Genetics"},{"issue":"4","key":"e_1_2_11_31_1","first-page":"110","article-title":"Infectious Salmon Anaemia in Salt Water Atlantic Salmon (\n                     Salmo salar\n                   L.) in New Brunswick, Canada","volume":"18","author":"Mullins J.","year":"1998","journal-title":"Bulletin of the European Association of Fish Pathologists"},{"issue":"2","key":"e_1_2_11_32_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/0042-6822(76)90178-1","article-title":"Proteolytic Cleavage of the Viral Glycoproteins and Its Significance for the Virulence of Newcastle Disease Virus","volume":"72","author":"Nagai Y.","year":"1976","journal-title":"Virology"},{"key":"e_1_2_11_33_1","volume-title":"Polymerase Chain Reaction: Theory and Technology","author":"Pfaffl M. W.","year":"2019"},{"issue":"2","key":"e_1_2_11_34_1","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1128\/JVI.06375-11","article-title":"Marked Endotheliotropism of Highly Pathogenic Avian Influenza Virus H5N1 Following Intestinal Inoculation in Cats","volume":"86","author":"Reperant L. A.","year":"2012","journal-title":"Journal of Virology"},{"issue":"1","key":"e_1_2_11_35_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/jam.14567","article-title":"Infectious Salmon Anaemia Virus\u2014Molecular Biology and Pathogenesis of the Infection","volume":"129","author":"Rimstad E.","year":"2020","journal-title":"Journal of Applied Microbiology"},{"issue":"4","key":"e_1_2_11_36_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1034\/j.1600-0463.2002.100401.x","article-title":"Infectious Salmon Anaemia Virus","volume":"110","author":"Rimstad E.","year":"2002","journal-title":"APMIS"},{"issue":"11","key":"e_1_2_11_37_1","doi-asserted-by":"crossref","first-page":"5352","DOI":"10.1128\/JVI.75.11.5352-5356.2001","article-title":"Characterization of the Infectious Salmon Anemia Virus Genomic Segment That Encodes the Putative Hemagglutinin","volume":"75","author":"Rimstad E.","year":"2001","journal-title":"Journal of Virology"},{"issue":"2","key":"e_1_2_11_38_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.1365-2761.2008.00973.x","article-title":"Comparative Virulence of Infectious Salmon Anaemia Virus Isolates in Atlantic Salmon, Salmo salar L","volume":"32","author":"Ritchie R. J.","year":"2009","journal-title":"Journal of Fish Diseases"},{"issue":"4","key":"e_1_2_11_39_1","first-page":"115","article-title":"Infectious Salmon Anaemia (ISA) in the United Kingdom","volume":"18","author":"Rodger H.","year":"1998","journal-title":"Bulletin of the European Association of Fish Pathologists"},{"issue":"9","key":"e_1_2_11_40_1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1046\/j.1365-2761.2003.00473.x","article-title":"Relative Resistance of Pacific Salmon to Infectious Salmon Anaemia Virus","volume":"26","author":"Rolland J. B.","year":"2003","journal-title":"Journal of Fish Diseases"},{"key":"e_1_2_11_41_1","first-page":"O\u201079","volume-title":"Diseases of Fish and Shellfish, 11th International Conference of the European Association of Fish Pathologists, St Julian's, Malta","author":"Schyth B. D.","year":"2003"},{"key":"e_1_2_11_42_1","doi-asserted-by":"crossref","first-page":"934809","DOI":"10.3389\/fnbeh.2022.934809","article-title":"The Effect of Fish Density and Tank Size on the Behavior of Adult Zebrafish: A Systematic Analysis","volume":"16","author":"Shishis S.","year":"2022","journal-title":"Frontiers in Behavioral Neuroscience"},{"key":"e_1_2_11_43_1","first-page":"133","article-title":"Development, Application and Validation of a Taqman Real\u2010Time RT\u2010PCR Assay for the Detection of Infectious Salmon Anaemia Virus (ISAV) in Atlantic Salmon (\n                     Salmo salar\n                  )","volume":"126","author":"Snow M.","year":"2006","journal-title":"Developments in Biologicals"},{"issue":"6","key":"e_1_2_11_44_1","first-page":"252","article-title":"Investigation Into the Potential for Seawater Rainbow Trout (\n                     Oncorhynchus mykiss\n                  ) to Act as Vectors of Infectious Salmon Anaemia Virus (ISAV)","volume":"21","author":"Snow M.","year":"2001","journal-title":"Bulletin of the European Association of Fish Pathologists"},{"issue":"1","key":"e_1_2_11_45_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0044-8486(00)00588-3","article-title":"Comparative Susceptibility of Arctic Char (\n                     Salvelinus alpinus\n                  ), Rainbow Trout (\n                     Oncorhynchus mykiss\n                  ) and Brown Trout (\n                     Salmo trutta\n                  ) to the Scottish Isolate of Infectious Salmon Anaemia Virus","volume":"196","author":"Snow M.","year":"2001","journal-title":"Aquaculture"},{"key":"e_1_2_11_46_1","first-page":"109","article-title":"Infectious Anaemia in Atlantic Salmon (\n                     Salmo salar\n                   L.)","volume":"8","author":"Thorud K.","year":"1988","journal-title":"Bulletin of the European Association of Fish Pathogists"},{"issue":"1","key":"e_1_2_11_47_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1172\/JCI44947","article-title":"Virulence Determinants of Pandemic Influenza Viruses","volume":"121","author":"Tscherne D. M.","year":"2011","journal-title":"Journal of Clinical Investigation"},{"issue":"5","key":"e_1_2_11_48_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1354\/vp.08-VP-0215-K-BC","article-title":"Pathology and Virus Distribution in Chickens Naturally Infected With Highly Pathogenic Avian Influenza A Virus (H7N7) During the 2003 Outbreak in The Netherlands","volume":"46","author":"Riel D.","year":"2009","journal-title":"Veterinary Pathology"},{"issue":"12","key":"e_1_2_11_49_1","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.3390\/v14122773","article-title":"Defective Interfering Particles of Influenza Virus and Their Characteristics, Impacts, and Use in Vaccines and Antiviral Strategies: A Systematic Review","volume":"14","author":"Wu M.","year":"2022","journal-title":"Viruses"}],"container-title":["Journal of Fish Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jfd.70291","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jfd.70291","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jfd.70291","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:25:48Z","timestamp":1790072748000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jfd.70291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":48,"alternative-id":["10.1111\/jfd.70291"],"URL":"https:\/\/doi.org\/10.1111\/jfd.70291","archive":["Portico"],"relation":{},"ISSN":["0140-7775","1365-2761"],"issn-type":[{"value":"0140-7775","type":"print"},{"value":"1365-2761","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"assertion":[{"value":"2026-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70291"}}