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

BMC Genomics. 2016 May 23;17:390. doi: 10.1186/s12864-016-2739-6.

Abstract

Background: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphavirus / physiology*
  • Animals
  • Cell Line
  • Fish Proteins / genetics
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation
  • Gene Expression Regulation, Viral / drug effects
  • Gene Regulatory Networks* / drug effects
  • Interferon Type I / pharmacology
  • Janus Kinases / genetics
  • MAP Kinase Signaling System / drug effects
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / virology
  • STAT Transcription Factors / genetics
  • Salmonidae / immunology
  • Salmonidae / virology*
  • Viral Structural Proteins / genetics*
  • Virus Replication

Substances

  • Fish Proteins
  • Interferon Type I
  • STAT Transcription Factors
  • Viral Structural Proteins
  • Janus Kinases