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

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.

• Authors: Cheng Xu, Øystein Evensen, Hetron Mweemba Munang'andu
• Journal: BMC genomics (BMC Genomics) Vol. 17 Pg. 390 (05 23 2016) ISSN: 1471-2164 [Electronic] England
• PMID: 27215196 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, metabolism, virology)
• STAT Transcription Factors (genetics)
• Salmonidae (immunology, virology)
• Viral Structural Proteins (genetics)
• Virus Replication