Health Science Reviews

By Dean Brink

If you were to pick any point in human history to travel to, you would almost instantly encounter a virus just as you stepped out of the time machine. These things are everywhere and infect just about every form of life on earth. Most people know at least something about viruses, especially some of the more infamous ones, though far fewer have heard of their minimalist cousins: viroids.

Viroids are currently the smallest known infectious agent, responsible for a variety of plant related diseases like potato spindle tuber disease. Unlike viruses – which generally contain two core components, genetic material and a protein bubble or capsid to hold that material – viroids consist exclusively of a small length of circular, single-stranded RNA only around 300 nucleotides long. These genomes do not actually encode for any proteins but can fold into secondary structures that hijack cellular machinery and cause disease. Given their simplicity, most tend to regard viroids as a kind of living fossil; they are remnants of the earliest scraps of RNA that assembled before the first cell formed, which have been floating around and persisting until today.

This traditional view may not be entirely accurate though, particularly considering recent studies done involving ambiviruses, a group of infectious agents found in fungi that appear to contain both viroid and virus elements! These elements were investigated in a recent study where the authors wanted to do a large-scale screening of publicly available RNA libraries to look for novel viroid-like elements, with a particular focus on what was similar to ambiviruses.

The researchers first used metatranscriptomic software like INFERNAL to identify over 32,000 novel viroid-like elements! They then compared these elements to what ambiviruses had and found that both contained ribozymes – a kind of secondary structure viroids are known to form, and which is dependent on extremely specific sequences of RNA being present. They then used the predictive programmes AlphaFold2 and MUSCLE to guess what proteins are made by ambiviruses and found they coded for a conserved RNA-dependent RNA-polymerase, a protein that is characteristic of antisense RNA viruses. Taken together, it seems that ambiviruses have a backbone made from a viroid, with a viral gene fused into it.

So, what does this all mean exactly? These findings show that our current understanding of viroids is not complete, there are many more out there we don’t know much about and there are potential more unique versions of them, like in these ambivirus hybrids. Further study into these tiny pathogens could provide both practical benefits, by preventing certain crop diseases, and help give a better understanding of life in the prebiotic era. Though I have to admit, looking at fossils of dinosaurs would probably be slightly more interesting to most people.

References: Forgia, M., Navarro, B., Daghino, S., Cervera, A., Gisel, A., Perotto, S., … & De La Peña, M. (2023). Hybrids of RNA viruses and viroid-like elements replicate in fungi. Nature Communications, 14(1), 2591