Abstract

The basis of pathogenicity of viral haemorrhagic septicaemia virus (VHSV) was analysed in the transcriptome of a rainbow trout cell line inoculated with pathogenic and non-pathogenic VHSV isolates. Although both VHSV isolates showed similar viral replication patterns, the number of differentially expressed genes was 42-fold higher in cells inoculated with the non-pathogenic VHSV at 3 h post inoculation (hpi). Infection with the non-pathogenic isolate resulted in Gene Ontologies (GO) enrichment of terms such as immune response, cytokine-mediated signalling pathway, regulation of translational initiation, unfolded protein binding, and protein folding, and induced an over-representation of the p53, PPAR, and TGF-β signalling pathways. Inoculation with the pathogenic isolate resulted in the GO enrichment of terms related to lipid metabolism and the salmonella infection KEGG pathway involved in the rearrangement of the cytoskeleton. Antiviral response was evident at 12hpi in cells infected with the pathogenic isolate. Overall, the data showed a delay in the response of genes involved in immune responses and viral sensing in cells inoculated with the pathogenic isolate and suggest transcriptional shutoff and immune avoidance as a critical mechanism of pathogenicity in VHSV. These pathways offer opportunities to further understand and manage VHSV pathogenicity in rainbow trout.

Highlights

  • Viral haemorrhagic septicaemia (VHS) is a notifiable fish disease by the World Organization for Animal Health (OIE)

  • Our results revealed the presence of immune evasion mechanisms, and the role of the unfolded protein response (UPR) in viral haemorrhagic septicaemia virus (VHSV) pathogenicity, highlighting the potential for these to be used as molecular targets for novel therapeutics

  • The present study showed that unfolded protein binding and protein folding processes were activated only in cells inoculated with the non-pathogenic VHSV despite both viruses replicating at the same rate

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Summary

Introduction

Viral haemorrhagic septicaemia (VHS) is a notifiable fish disease by the World Organization for Animal Health (OIE). From when it was first reported as a disease affecting freshwater rainbow trout in Europe in the 1930s [1], it was estimated to result in economic losses of between USD 60 and 150 million annually for the Western European and Norwegian aquaculture industry, before sanitation programmes were successfully implemented in the latest 1960s [2]. VHSV is a single-stranded RNA novirhabdovirus within the family Rhabdoviridae. It consists of an enveloped, non-segmented, negative-sense, genome of approximately. The majority of VHSV isolates causing outbreaks in freshwater rainbow trout farms belong to sub-lineage Ia and Ic [8,9]

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