Evaluation of the potential roles of microribonucleic acids in the interaction of rainbow trout (Oncorhynchus mykiss) with Viral hemorrhagic septicemia virus

Micro ribonucleic acids (miRNAs) are endogenous, 18-22-nucleotide non-coding RNAs that potently mediate post-transcriptional silencing of a broad range of genes. They are emerging as critical regulators of a broad spectrum of biological processes, including immune responses and host-pathogen interactions. Some miRNAs in mammals have been shown to directly inhibit viruses, whereas other cellular miRNAs can be co-opted by viruses to promote viral replication or evade host immune responses. We have previously observed that two miRNAs known from zebrafish, miR-462 and miR-731, were the most highly expressed miRNAs in rainbow trout liver following Viral hemorrhagic septicemia virus (VHSV) infection. These miRNAs were also upregulated in the liver and muscle (vaccination site) of fish vaccinated with a DNA vaccine encoding the glycoprotein of VHSV. Recent studies further suggest that the expression of these miRNAs is induced by interferons. In order to investigate the potential role(s) of miRNA-462 and miRNA-731 in host-pathogen interactions, we designed synthetic oligonucleotides called antagomiRs or anti-miRNAs to silence these two miRNAs. These antagomiRs were injected intraperitonealy into rainbow trout fingerlings followed by exposure of the fish to VHSV. Development of disease and levels of infection were analyzed and compared to data from fish treated with control miRNAs. Further analysis of the effect of anti-miRNAs in cell culture will be performed.