Uncovering the virosphere
We know that viruses are everywhere and there are a lot of them. But how little we know about them is only now becoming clear. In particular, RNA viruses seem to have many surprises to offer. The reasons for this lack of knowledge, the recent progress made, and the implications of what we are finding are clearly summarised in this fascinating review by Zhang and colleagues.
How much do we know?
Fairly little. Particularly for RNA viruses. This is because we tend to focus on viruses that are pathogenic for us or for the animal and plant species that we are most familiar with, as well as for technical reasons. Perhaps one of the main obstacles is that, although we are quite good at recognizing viral sequences that are distinct from the genome of other organisms, many viruses have evolved in a constant exchange of genetic information with the host, and classifying host-like sequences as viral is not straightforward.
What’s new?
Despite these limitations, large-scale RNA sequencing of the tissues of various species (after subtracting rRNA) – known as meta-transcriptomics – has massively advanced the field by unbiasedly revealing entire new viral RNA genomes. One of the biggest surprises was the remarkable number and diversity of RNA viruses in invertebrate hosts. Invertebrates (generally meaning arthropods) turned out to be not only vectors for human viruses (e.g., alphaviruses or flaviviruses) but also hosts for RNA virus recombination and evolution. This is probably helped by the large population sizes arthropods, an ecological prerequisite for viral diversity. These viruses rarely cause disease in their host, which raises an interesting question on the determinants of pathogenicity vs. tolerance.
The important point is that RNA viruses, far from relying exclusively on high mutation rate, also evolve through more complex processes, such as gene duplication and loss, genomic rearrangement, and lateral gene transfer, where entire cellular genes can be found integrated into the viral genome.
Surprising Flaviviridae
Interesting surprises come from the world of Flaviviridae and flavi-like viruses. Several insect-specific flaviviruses have now been identified, carrying genomes as long as 26 kb, sometimes organized in multiple segments that might even be delivered in different viral particles. This is interesting, as viral families are characterized by a specific segmentation type, but these new findings place segmented and non-segmented viruses within the same family.
As often happens in virology, these studies reveal an additional level of complexity of which we know very little about. In addition to the interesting taxonomic implications, where new viral species will fill up evolutionary gaps between viral groups, a deeper knowledge of the evolution of arthropod viruses can shed light on fundamental dynamics of host-pathogen interaction. How do RNA viruses exploit genomic rearrangements to promote a tolerogenic vs. a pathogenic status? What are the implications for cross-species transmission? How much has the development of adaptive immunity in vertebrate hosts forced RNA virus rearrangement into invertebrates? What are the advantages of a segmented over a non-segmented genome? Moreover, and importantly, can any of these discoveries help our understanding of human RNA pathogens?
As the authors suggest, more studies aided by future technological advances might overcome the current challenges and are likely to provide a clearer view of this compelling world.
