Giant Viruses: Their Stories, and Ours

There’s something… disturbing, to say the least, about viruses.

Viruses have no standard organelles, no ability to reproduce on their own, and don’t have any metabolic activity (not like they need it).  They lack all the “machinery” a living cell uses, like ribosomes essential for protein production andor mitochondria required to generate usable energy for the cell. Instead, they act as obligate parasites, hijacking those of actual living cells for reproduction and metabolism. They’re something that straddles the line between biological organism and chemical amalgamation. We have no idea where they came from. Getting attacked by one can be fatal. They’re nothing more than little bags of DNA wrapped up in protein shells called capsids are too small to be seen even under a microscope. It’s like getting beaten up by a very angry piece of furniture.

Can you tell I have a bone to pick with the concept?

So what happens when we finally find a virus that throws these assumptions under the bus? Well, after a thorough search combing the various microbiota of the world, we have our candidate, or rather, candidates. And these viruses seem to challenge the common knowledge about their kind that we took for granted.

Meet mimivirus, the most iconic member of Mimiviridae, a family of giant viruses (Duponchel, 2019). Initially mistaken for a bacteria because it could be identified via a bacteria-locating test called a “gram stain”, our good friend here is so bodaciously chunky that it can be infected by other viruses known as satellite viruses (specifically, sputnik viruses – astronomy geeks will appreciate the reference.) In the image above, the satellites are indicated by arrows.

Mimivirus, or “mimicking microbe” virus, is 400 nanometers in size, and for a while it was the biggest virus known to man. It may contribute to pneumonia, but that conclusion is thus far still indefinite (La Scola, 2005).

The current title of largest virus belongs to Megaklothovirus horridgei, a horrid beast that grows up to 3.9 micrometres – twice the size of E. coli, our familiar bacterial friend (Barthelemy, 2019). However, this virus has mainly been isolated from arrow worms, meaning we should be safe. Hopefully. We haven’t actually studied it very much.

Giant viruses actually have a very unique ability when it comes to infecting cells. While organisms like amoeba have defence systems to capture and kill invading viruses, it seems that this instead helps trigger a little piece of viral technology in giant viruses called the “stargate”, opening up a system of 5 “legs” that form a star-shaped opening for viral DNA to spew out and infect the host (York, 2020). Pretty neat.

This is where things stop being normal and start getting freaky.

You see, most viruses are quite minimalist. They take along only what they need and travel light, opting to be a total parasite and get the rest of their reproductive equipment from their hapless hosts.

Giant viruses are different. These contain a good amount of cellular machinery that actual living cells have – ribosomal proteins, transfer RNA (which matchmakes amino acids to sequences on messenger RNA), factors for DNA replication… in short, just about most things that make up a cell’s replicative machinery, save for the actual ribosome itself.

Are they alive? The question becomes difficult here. Are we going to define life as the possession of ribosomes, mitochondria, and a cell membrane? Neither yes nor no seem particularly satisfactory.

Another tricky question: giant viruses like Pandoravirus have genes that are unlike anything else we see in the living world, and they’re distinct, too, from other viruses. These genes, known as ORFans, are distinct from the rest of the known homology (Aherfi, 2018). In other words, are giant viruses really viruses?

What this implies is nothing short of revolutionary. We may well have stumbled upon a missing branch of the tree of life! One hypothesis is that these giant viruses used to be a category of cellular life of their own that gradually reduced their own complexity, opting instead for a parasitic lifestyle, and eventually ended up becoming viruses by shedding the main hallmarks of living cells (Legendre, 2012). Others opine that no such branch exists, and that the viruses were formed by other means, like picking up DNA from other viruses and their hosts (Yutin, 2014).

Could this tell us about the origins of other viruses? Or did they come about via entirely different processes? We have so many questions, and their answers are so important they may even shed light about the origin of life itself on our planet. After all, these giant viruses’ history could dissolve the boundary between living and non-living “organisms” and force us to redraw that line.

Despite the undeniable intrigue of giant virus research, we are no closer to a satisfactory conclusion. Giant viruses are miniscule on institutional research budgets simply because they don’t cause much in the way of disease. With urgent research on how to directly predict, avert and combat pandemics in the making, (re-)defining life is arguably not quite so important. Even though climate change raises the worry that viruses encased in ice, like pithoviruses, will be released and create new diseases, whether this will drive further research into the dangers they can pose is up in the air (Yong, 2014), especially since the risks of such an event occurring are dwarfed by the damage caused by the viruses already plaguing us (pun intended), including recent pandemics like Covid. The giants just aren’t very relevant in the face of practical concerns. Despite this, one can’t help but wonder what these behemoths are concealing in their genetic history.

Giant viruses’ stories aren’t just about their narrative, but also about ours. Their epilogue may be our prologue. If their mysteries are ever solved, we may be one step closer to imagining the Earth as it was when life was first born.

References

Aherfi, S., Andreani, J., Baptiste, E., Oumessoum, A., Dornas, F. P., Andrade, A. C. D. S. P., Chabriere, E., Abrahao, J., Levasseur, A., Raoult, D., La Scola, B., & Colson, P. (2018). A Large Open Pangenome and a Small Core Genome for Giant Pandoraviruses. Frontiers in microbiology, 9, 1486. https://doi.org/10.3389/fmicb.2018.01486

Duponchel S, Fischer MG (2019) Viva lavidaviruses! Five features of virophages that parasitize giant DNA viruses. PLoS Pathog 15(3): e1007592. https://doi.org/10.1371/journal.ppat.1007592

La Scola B, Marrie T, Auffray J, Raoult D (2005). "Mimivirus in pneumonia patients". Emerg Infect Dis. 11 (3): 449–52. doi:10.3201/eid1103.040538.

Legendre, M., Arslan, D., Abergel, C., & Claverie, J. M. (2012). Genomics of Megavirus and the elusive fourth domain of Life. Communicative & integrative biology, 5(1), 102–106. https://doi.org/10.4161/cib.18624

Roxane-Marie Barthelemy, Taichiro Goto, Eric Faure. Serendipitous Discovery in a Marine Invertebrate (Phylum Chaetognatha) of the Longest Giant Viruses Reported till Date. Virology: Current Research , 2019, 3 (1). ffhal-02010229f

Yong, Ed (2014). "Giant virus resurrected from 69,000-year-old ice". Nature. doi:10.1038/nature.2014.14801

York, A. Opening the stargate. Nat Rev Microbiol 18, 363 (2020). https://doi.org/10.1038/s41579-020-0388-x

Yutin, N., Wolf, Y. I., & Koonin, E. V. (2014). Origin of giant viruses from smaller DNA viruses not from a fourth domain of cellular life. Virology, 466-467, 38–52. https://doi.org/10.1016/j.virol.2014.06.032

Image Credit: https://www.the-scientist.com/ancient-giant-virus-discovered-37851