Pathogenic Mechanism of a Highly Virulent Infectious Hematopoietic Necrosis Virus in Head Kidney of Rainbow Trout (<i>Oncorhynchus</i> <i>mykiss</i>) Analyzed by RNA-Seq Transcriptome Profiling

Abstract

Infectious hematopoietic necrosis virus (IHNV) is a pathogen that causes high rates of mortality in salmonid fishes. Therefore, an RNA-seq-based transcriptome analysis was performed in the head kidney of rainbow trout infected with a highly virulent IHNV strain to understand the pathogenesis of and defense strategies for IHNV infection in rainbow trout. The results showed that the numbers of DEGs were 618, 2626, and 774 (control vs. IHNV) on days 1, 3, and 5, respectively. Furthermore, the enrichment analysis of gene ontology (GO) annotations to classify DEGs showed that GO terms considerably associated with DEGs were gluconeogenesis, inflammatory response, and cell adhesion in the Biological Process (BP) category, apical plasma membrane, extracellular matrix (ECM) in the Cellular Component category, and transporter activity, integrin binding, and protein homodimerization activity in the Molecular Function category, on days 1, 3, and 5, respectively. Notably, GO terms in the BP category, including the negative regulation of type I interferon production and positive regulation of interleukin-1β secretion, were commonly identified at all time points. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, complement and coagulation cascades were commonly identified at all time points. Importantly, the widely recognized GO terms and KEGG pathways extensively linked to DEGs were related to energy metabolism on day 1, the immune response on day 3, and cell proliferation on day 5. Furthermore, protein–protein interaction networks and centrality analysis showed that the metabolism and signaling transduction pathways were majorly upregulated. Conclusively, the virulent IHNV infection drives pathogenesis by activating the metabolic energy pathway for energy use for viral replication, facilitating necrosis through autophagy, and causing a shutoff response of the host immune system through the downregulation of type I IFN at the initial stage of infection.

Keywords

• IHNV
• pathogenesis
• transcriptome
• rainbow trout