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

BackgroundThe 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.ResultsConcurrent 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.ConclusionData 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.

Immune gene profiles in Atlantic salmon (salmo salar L.) post-smolts infected with SAV3 by bath-challenge show a delayed response and lower levels of gene transcription compared to injected fish

“…The negligible IFNa response in the BI group has been observed previously in cohabitation infections with SAV [14]. In a recent study, recombinant IFNa applied simultaneously with SAV3 to a TO cell culture was able to induce the rapid transcription of ISGs resulting in a 20-fold reduction of SAV3 RNA compared to cells not treated with IFNa [36]. Clearly the more rapid the induction of IFNa the better protection the host has against SAV.…”

Atlantic salmon post-smolts adapted for a longer time to seawater develop an effective humoral and cellular immune response against Salmonid alphavirus

“…The high transcript abundance of SOCS1 has been suggested to be a consequence of SAV infection and may be a survival strategy for the virus. Increasing SOCS1 mRNA expression may subsequently inhibit signal transduction via the JAK/STAT pathway and may contribute to viral replication [31,32]. In our previous study, we observed a reduction in ISG and Mx expression in the IM-B group [19] that partially may be due to up-regulation of the SOCS1 after SAV infection.…”

Environmental Viral Metagenomics Analyses in Aquaculture: Applications in Epidemiology and Disease Control

“…This is mainly because there has been a general lack of appropriate tools able to identify and characterize viruses collected from environmental samples. However, the emergence of high throughput next generation sequencing (NSG) in recent years has not only enhanced our understanding of host responses to viral infections (Chu et al, 2015; Dahle et al, 2015; Xu et al, 2015, 2016a,b; Liu et al, 2016), but it has opened a great avenue for identification of viruses found in different aquatic environments using metagenomics analyses (Suttle, 2005, 2007; Djikeng et al, 2009; Kim et al, 2015). Viral metagenomics is a culture independent sequencing tool able to identify a large number of viral genomes from the same sample at the same time without prior knowledge of genomic sequences of the viruses to be identified (Handelsman, 2004; Bibby, 2013).…”