Trans-Acting RNA-RNA Interactions in Segmented RNA Viruses

Abstract

RNA viruses represent a large and important group of pathogens that infect a broad range of hosts. Segmented RNA viruses are a subclass of this group that encode their genomes in two or more molecules and package all of their RNA segments in a single virus particle. These divided genomes come in different forms, including double-stranded RNA, coding-sense single-stranded RNA, and noncoding single-stranded RNA. Genera that possess these genome types include, respectively, Orbivirus (e.g., Bluetongue virus), Dianthovirus (e.g., Red clover necrotic mosaic virus) and Alphainfluenzavirus (e.g., Influenza A virus). Despite their distinct genomic features and diverse host ranges (i.e., animals, plants, and humans, respectively) each of these viruses uses trans-acting RNA-RNA interactions (tRRIs) to facilitate co-packaging of their segmented genome. The tRRIs occur between different viral genome segments and direct the selective packaging of a complete genome complement. Here we explore the current state of understanding of tRRI-mediated co-packaging in the abovementioned viruses and examine other known and potential functions for this class of RNA-RNA interaction.

Keywords: RNA packaging; RNA structure; RNA virus; RNA–RNA interactions; bluetongue virus; influenza virus; red clover necrotic mosaic virus; reovirus; segmented virus.

Figure 1

Genome-related structures for Influenza A virus. (A) Linear representation of influenza A virus (IAV) genome segments, labeled 1 to 8 (left), along with corresponding proteins encoded by each (right). (B) Schematic representation of a generic IAV vRNP complex with relevant structural features labelled. Not to scale. (C) Axial view of 7+1 arrangement of vRNPs depicting their parallel alignment inside IAV particles. (D) Predicted RNA secondary structures of interacting RNA regions in vRNP 8 and vRNP 2 (left) and their in trans RNA–RNA interaction (right) that mediates vRNP association [9]. The local RNA secondary structures (left) are predicted to extend from their respective vRNPs (as shown in B, labeled, RNA secondary structure), thereby facilitating nucleation the interaction.

Figure 2

Summary of positions in IAV genome segments involved in inter-segment interactions in different IAV strains [24]. The eight segments are shown aligned in a circle with inter-segment interactions represented by curved coloured lines. See legends for correlations of interactions between IAV strains. (A) WSN (H1N1). (B) PR8 (H1N1). (C) Udorn (H3N2).

Figure 3

Genome-related structures for Bluetongue virus. (A) Linear representation of the BTV genome segments, labeled S1 to S10 (left), along with corresponding proteins encoded by each (right). Smaller segments are individually color-coded. (B) Schematic representation depicting the number of predicted interactions (white circles) occurring between different viral mRNAs (color-coded circles) during early RNA–RNA complex assembly in BTV [37].

Figure 4

Genome-related structures for Red clover necrotic mosaic virus. (A) Linear representation of the RCNMV genome segments, labeled 1 and 2 (left), along with corresponding proteins encoded by each (right). (B) Schematic representation of RCNMV RNA1 and RNA2 and their encoded proteins (boxes). The relative location of the TA and TABS in each genome segment is indicated by a dark green bar. Sg mRNA transcription occurs via production of a sg mRNA-sized (−)RNA intermediate (red), that is then used as a template to transcribe the sg mRNA. (C) Depiction of the sequences (highlighted in green) that are involved in the TA–TABS tRRI between RCNMV RNA1 and RNA2 that activates sg mRNA transcription [47].