Virtual screening of gene expression regulatory sites in non-coding regions of the infectious salmon anemia virus

Abstract

BackgroundMembers of the Orthomyxoviridae family, which contains an important fish pathogen called the infectious salmon anemia virus (ISAV), have a genome consisting of eight segments of single-stranded RNA that encode different viral proteins. Each of these segments is flanked by non-coding regions (NCRs). In other Orthomyxoviruses, sequences have been shown within these NCRs that regulate gene expression and virulence; however, only the sequences of these regions are known in ISAV, and a biological role has not yet been attributed to these regions. This study aims to determine possible functions of the NCRs of ISAV.ResultsThe results suggested an association between the molecular architecture of NCR regions and their role in the viral life cycle. The available NCR sequences from ISAV isolates were compiled, alignments were performed to obtain a consensus sequence, and conserved regions were identified in this consensus sequence. To determine the molecular structure adopted by these NCRs, various bioinformatics tools, including RNAfold, RNAstructure, Sfold, and Mfold, were used. This hypothetical structure, together with a comparison with influenza, yielded reliable secondary structure models that lead to the identification of conserved nucleotide positions on an intergenus level. These models determined which nucleotide positions are involved in the recognition of the vRNA/cRNA by RNA-dependent RNA polymerase (RdRp) or mRNA by the ribosome.ConclusionsThe information obtained in this work allowed the proposal of previously unknown sites that are involved in the regulation of different stages of the viral cycle, leading to the identification of new viral targets that may assist future antiviral strategies.

RNA Viruses: RNA Roles in Pathogenesis, Coreplication and Viral Load

“…The viral RNA 3’- and 5’-end structure and mRNA transcription of infectious salmon anaemia virus resemble those of influenza viruses [ 22 ]. The aligned Non-Coding Region (NCR) sequences from ISAV isolates were compared with those from influenza virus, and consensus sequences were found, based on conserved regions identified in the consensus sequence [ 23 ]. This hypothetical structure, together with a comparison with influenza viruses, yielded reliable secondary structure models that lead to identification of conserved nucleotide positions at inter-genus level to determine which nucleotide positions are involved in the recognition of the vRNA/cRNA by RNA-dependent RNA polymerase (RdRp) or mRNA by the ribosome.…”