title: A de novo transcriptome analysis shows that modulation of the JAK-STAT signaling pathway by salmonid alphavirus subtype 3 favors virus replication in macrophage/dendritic-like TO-cells.
abstract: The Janus kinase (Jak) and signaling transducer activator of transcription (Stat) pathway mediates the signaling of genes required for cellular development and homeostasis. To elucidate the effect of type I IFN on the Jak/stat pathway in salmonid alphavirus subtype 3 (SAV3) infected macrophage/dendritic like TO-cells derived from Atlantic salmon (Salmo salar L) headkidney leukocytes, we used a differential transcriptome analysis by RNA-seq and the Kyoto encyclopedia of genes and genomes (KEGGs) pathway analysis to generate a repertoire of de novo assembled genes from type I IFN treated and non-treated TO-cells infected with SAV3.
  
  
  
  Concurrent SAV3 infection with type I IFN treatment of TO-cells suppressed SAV3 structural protein (SP) expression by 2log10 at 2 days post infection compared to SAV3 infection without IFN treatment which paved way to evaluating the impact of type I IFN on expression of Jak/stat pathway genes in SAV3 infected TO-cells. In the absence of type I IFN treatment, SAV3 downregulated several Jak/stat pathway genes that included type I and II receptor genes, Jak2, tyrosine kinase 2 (Tyk2), Stat3 and Stat5 pointing to possible failure to activate the Jak/stat signaling pathway and inhibition of signal transducers caused by SAV3 infection. Although the suppressor of cytokine signaling (SOCS) genes 1 and 3 were upregulated in the IFN treated cells, only SOCS3 was downregulated in the SAV3 infected cells which points to inhibition of SOCS3 by SAV3 infection in TO-cells.
  
  
  
  Data presented in this study shows that SAV3 infection downregulates several genes of the Jak/stat pathway, which could be an immune evasion strategy, used to block the transcription of antiviral genes that would interfere with SAV3 replication in TO-cells. Overall, we have shown that combining de novo assembly with pathway based transcriptome analyses provides a contextual approach to understanding the molecular networks of genes that form the Jak/stat pathway in TO-cells infected by SAV3.
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Section of Aquatic Medicine and Nutrition, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, P.O Box 8146, Oslo, NO-0033 Dep, Norway.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Section of Aquatic Medicine and Nutrition, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, P.O Box 8146, Oslo, NO-0033 Dep, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Evensen
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Section of Aquatic Medicine and Nutrition, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, P.O Box 8146, Oslo, NO-0033 Dep, Norway. hetroney.mweemba.munangandu@nmbu.no.
authors.forename: Hetron Mweemba
authors.initials: HM
authors.lastname: Munang'andu
mesh_terms: D000524:Alphavirus / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D029941:Fish Proteins / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D007370:Interferon Type I / Q000494:pharmacology; D053612:Janus Kinases / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D050791:STAT Transcription Factors / Q000235:genetics; D012487:Salmonidae / Q000276:immunology / Q000821:virology*; D015678:Viral Structural Proteins / Q000235:genetics*; D014779:Virus Replication
chemical_list: D029941:Fish Proteins; D007370:Interferon Type I; D050791:STAT Transcription Factors; D015678:Viral Structural Proteins; D053612:Janus Kinases