Kurzgesagt – In a Nutshell
Sources – Girus
We thank following experts for their critical reading and input:
Frank Aylward
Asst. Prof. of Biological Sciences, Virginia Tech
Nathan Rubien
Full-time Lecturer, University of Massachusetts
Frank Scarano
Professor and Dept. Chair, University of Massachusetts
Nitai Steinberg
Science communicator
– Hidden in the microverse all around you, there is a merciless war being fought by the true rulers of this planet, microorganisms. Amoebae, protists, bacteria, archaea and fungi compete for resources and space.
Microorganisms are true rulers of the planet, there would be no air to breath, no clean water or no soil to cultivate. They are everywhere and all around and inside us, and have a great part regulating earth’s ecosystems.
#Heip et al., Marine Biodiversity and Ecosystem Functioning, 2016.
https://www.researchgate.net/publication/306030378_Marine_Biodiversity_and_Ecosystem_Functioning
Quote: “In the ocean, microbes – or organisms from 0.2 to 100μm – are very abundant. It has been calculated that they account for about half of the biomass on planet Earth. In the ocean, Bacteria and Archaea account for billions of tonnes of carbon (estimates range from 3 to 14 billion) while, in contrast, the entirety of mankind on Earth only accounts for about 0.03 billion tonnes of carbon. In a drop (one millilitre) of seawater, one can find 10 million viruses, one million bacteria and about 1,000 small protozoans and algae (called “protists”).”
It would not be possible to cover their extensive role here, you can refer to the following journal issue for a glimpse of microorganisms’ impact on the environment, from climate change to sulfur and nitrogen cycles:
#Nature Reviews Microbiology, Microbial biogeochemistry, 2018
https://www.nature.com/collections/qbqscspvks
Microorganisms circulate and recycle organic molecules across the lithosphere, atmosphere, hydrosphere and biosphere. They provide all animals and plants with the biogeochemical balance that is essential to life. And as most rulers, they are as merciless as they are generous. They come up with various methods and tools to fight fiercely for the resources essential for their survival – from secreting chemicals to harvest nutrients, getting rid of costly genes and obtaining their products from other microorganisms, poisoning neighbouring cells, or preventing others from colonizing.
Following paper reviews these wide range of mechanisms:
#Ghoul and Mitri, The Ecology and Evolution of Microbial Competition, 2016
Bacteria, for instance, can produce lethal chemicals against rivaling colonies. They can stop the growth of sibling colonies nearby or even kill them through these chemicals. This way they can preserve the resources in the environment for themselves.
For example, the study below found that sibling bacterial colonies produce two different proteins to regulate the competition for resources. One protein called subtilisin promotes the growth of a normal bacterial colony (image C). However, once colonies grow big enough and subtilisin reaches above a certain threshold in the interface between the two colonies (image A), a second protein is released this time. Subtilisin cuts this initially harmless protein into smaller pieces and thereby unlocks the lethal power in one of the smaller chunks which kills the rivaling cells.
#Be’er et al., Lethal protein produced in response to competition between sibling bacterial colonies, 2010.
https://www.pnas.org/content/107/14/6258
Quote: “Sibling Paenibacillus dendritiformis bacterial colonies grown on low-nutrient agar medium mutually inhibit growth through secretion of a lethal factor. ”
– Not even being alive, they are the tiniest, most abundant and deadliest beings on earth, killing trillions every day.
Among all the other microorganisms, viruses are the most abundant:
#Koonin and Dolja, A virocentric perspective on the evolution of life, 2013.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326007/
Quote: “Over the last decade, studies of the distinct environmental viromes produced a completely unexpected conclusion: viruses are the most abundant biological entities on earth. This conclusion was substantiated by direct counting of virus particles and cells in marine samples (the environment harboring most of the Earth's biomass). These analyses consistently detect a 10–100 excess of virus particles over cells [3•, 17].”
In line with their abundance, they are also relentless mass murderers:
#Suttle, Marine viruses — major players in the global ecosystem, 2007.
https://www.nature.com/articles/nrmicro1750
Quote: “Every second, approximately 10^23 viral infections occur in the ocean. […] Viruses kill approximately 20% of the oceanic microbial biomass daily, which has a significant impact on nutrient and energy cycles. ”
– Considerably smaller than your cells or even bacteria, they are nothing but a hull, a tiny bit of genetic material and a few proteins.
Although viruses are quite diverse, they all share some basic properties: Possessing some type of genetic material - be it RNA or DNA- covered by a protein coat called capsid, being able to replicate only inside a host cell and, having a diameter of less than 200 nm – until giant viruses have been discovered of course. Another critical shared feature is that no viruses are known to contain ribosomes. So they can not produce their proteins without the machinery of the host cell. This does not only make them obligatory parasites but also obscures their status as being alive – since they do not perform metabolic processes similarly to living organisms we are used to.
#A World of Viruses, HMSC, 2021
https://hmsc.harvard.edu/world-viruses
Quote: “Viruses come in many different shapes and sizes, but all are made of two essential components: a core of genetic material, either DNA or RNA, which is surrounded by a protective protein coat called a capsid. Packaged together, a single virion comes in four different shapes: helical, polyhedral, spherical, and complex.”
Viruses come in all different sizes, from 20nm to 400nm and shapes:
The following is an interactive tool showing 3D models of viruses that caused human epidemics:
#HHMI Biointeractive, Virus Explorer
Following image shows relative sizes of some commonly known particles to put virus sizes in perspective:
#Visual capitalist, the relative size of particles, 2020.
– No metabolism, no way to propel themselves, no will or ambition. They float around aimlessly and hope to stumble upon a victim to infect and take over.
Viruses rely on the resources of the host cell to compensate for the metabolism that they lack to have independently themselves. They also do not have any means to move independently, though some viruses (plant viruses) produce movement proteins using the host cell’s resources and they can spread further from one infected cell to the next cell.
#Wessner D. R., The Origins of Viruses, 2010.
https://www.nature.com/scitable/topicpage/the-origins-of-viruses-14398218/
Quote: “Viruses do not, however, carry out metabolic processes. Most notably, viruses differ from living organisms in that they cannot generate ATP. Viruses also do not possess the necessary machinery for translation, as mentioned above. They do not possess ribosomes and cannot independently form proteins from molecules of messenger RNA. Because of these limitations, viruses can replicate only within a living host cell. Therefore, viruses are obligate intracellular parasites. According to a stringent definition of life, they are nonliving. Not everyone, though, necessarily agrees with this conclusion. Perhaps viruses represent a different type of organism on the tree of life — the capsid-encoding organisms, or CEOs.”
– Viruses are so simple that we are not sure if they should count as living things or not.
Whether viruses are alive or not is a question which has invoked different views. The answer partly depends on which conditions we take for an organism to be alive. Basic criteria to be considered as alive are being able to grow, reproduce, have a metabolism, keep homeostasis, respond to stimuli and evolve as a species. So viruses reproduce in some way since they replicate inside the host upon infection and they also evolve through the mutations. They are alive when these conditions are considered. However, they can not carry out metabolic processes independently of the host. They can not generate ATP and they do not have the means to produce proteins on their own since they do not possess ribosomes. Therefore, they can not be considered as alive based on this set of criteria. However, their partial satisfaction of the criteria also has left the scientists partial to the question. There has been a long lasting debate on the topic which takes new direction as new discoveries come in.
Below is a review on the different approaches to the question and the validity of the question itself:
#Koonin and Starokadomskyy. Are viruses alive? The replicator paradigm sheds decisive light on an old but misguided question, 2016.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406846/
– Some scientists consider viruses as alive.
Especially after the discovery of giant viruses, some scientists approach this view with new arguments and interpretations:
#Raoult and Forterre, Redefining viruses: lessons from Mimivirus, 2008.
https://pubmed.ncbi.nlm.nih.gov/18311164/
Quote: “Here, we propose to reinstall a primary dichotomy in the classification of the living world between REOs (ribosome encoding organisms) and CEOs (capsid encoding organisms). We conclude that two connected natural worlds have evolved in parallel. One form of life expresses ribosomes and comprises three domains: archaea, bacteria and eukarya. The other form of life expresses capsids that produce virions which infect REOs from each of these three domains.”
– Others think that the cells they infect are the actual living viruses, hybrid organisms called virocells, and the viral particles are more like seeds or spores.
#Claverie and Abergel, Mimivirus: the emerging paradox of quasi-autonomous viruses, 2010.
https://pubmed.ncbi.nlm.nih.gov/20696492/
Quote: “We thus proposed that the intracellular factory corresponds to the real virus, whereas the virion should be reappraised as the mere vehicle used to spread its genome from cell to cell [23,28,30]. Within this new conceptual framework, equating virus and virion is like confusing a seed with a tree, or an egg cell with a human being, even though both of them exhibit the same genome (Figure 2). This new way of looking at large DNA viruses infecting eukaryotes is making some progress in the community, where some authors extended it to viruses infecting Eubacteria or Archaebacteria with the ‘‘virocell’’ concept, whereby the infected host cell becomes the true virus [24,31].”
– And many others think viruses are just dead material.
#López-García, The place of viruses in biology in light of the metabolism- versus- replication- first debate, 2012.
https://pubmed.ncbi.nlm.nih.gov/23316568/
Quote: “There are many definitions of life and/or living organisms that incorporate more or less long lists of properties (Luisi 1998). However, when reduced to essentials, they can be aligned along the two historically opposed views on the origin of life, metabolist (cytoplasmist) versus geneticist (nucleocentric). For metabolist views – more popular among biochemists and physicists – the essential property of life is self-maintenance. Obviously, viruses do not conform to such a definition of life because they lack any form of metabolism. [...] For geneticist views, the essential properties of life are self-replication and evolution. Evolution is a consequence of imperfect replication generating variants upon which drift or natural selection can act. Viruses do evolve, but are unable to self-replicate. Consequently, this definition of life does not accommodate viruses either”
– The origin of viruses is a mystery, because how can something that needs victims to make more of itself emerge in the first place? There are many ideas.
Even though it is widely accepted now that viruses have descended from multiple ancestors instead of a single one, scientists have not yet reached a consensus on the ultimate origin of viruses. It is difficult to pin down their origin for mainly two reasons: Their genetic history is not easily traceable since they have very mobile genomes with high mutation rates, and they do not leave fossils behind. Three major scenarios have been suggested so far: 1- Virus early hypothesis states that viruses originate from primordial, precellular genetic elements, 2- Regression hypothesis suggests that viruses have evolved from cellular ancestors and lost cellular functions like translation along the way 3- Escape hypothesis states that some of the genes from cellular hosts achieved partial replicative autonomy and became viruses.
#Wessner, D. R. The Origins of Viruses. Nature Education, 2010.
https://www.nature.com/scitable/topicpage/the-origins-of-viruses-14398218/
Quote: “There is much debate among virologists about this question. Three main hypotheses have been articulated: 1. The progressive, or escape, hypothesis states that viruses arose from genetic elements that gained the ability to move between cells; 2. The regressive, or reduction, hypothesis asserts that viruses are remnants of cellular organisms; and 3. The virus-first hypothesis states that viruses predate or coevolved with their current cellular hosts.”
Following image illustrates these three hypotheses:
#Krupovic et al., Origin of viruses: primordial replicators recruiting capsids from hosts, 2019.
https://hal-pasteur.archives-ouvertes.fr/pasteur-02557191/document
– Viruses may have been essential steps in the emergence of life, or maybe they started out as escaped DNA from cells that became really good at making copies of themselves. Maybe they are the descendants of truly lazy parasites that let others do all the work for them?
As summarized above there are three main hypotheses on the origin of viruses. The first two, progressive and regressive hypotheses, propose that viruses followed cellular life.
Progressive hypothesis postulates that viruses are pieces of genetic material that acquired the ability of semi-autonomous replication and had enough mobility to escape the host cell. Therefore, the genetic bits escaped from bacteria, archaea and eukaryotic cells became bacterial, archeal and eukaryotic viruses, respectively. The common example that is put forward to support this hypothesis is the case of retroviruses. Retroviruses carry single-stranded RNAs as their genetic material which are converted to double-stranded DNA upon infection and merge into the DNA of the host cell. This way viral genes hack transcriptional and translational mechanisms of the host and further single stranded viral RNAs are produced. This mechanism resembles the mechanism of retrotransposons, the mobile genetic bits of eukaryotic genomes. Similarly, some retrotransposons show RNA mediated mobility and can insert themselves into new locations along the genome. It could be that precursors of viruses got liberated from a cell through a similar mechanism and then entered back in another one, starting effectively the first infectious cycle. Recently, this view has been updated to date the escape event to primordial cells, therefore well before the last universal cellular ancestor.
#Forterre and Krupovic, The Origin of Virions and Virocells: The Escape Hypothesis Revisited, 2012.
https://link.springer.com/chapter/10.1007%2F978-94-007-4899-6_3
Quote: “The first viruses probably originated in a world of cells already harbouring ribosomes (ribocells), but well before the Last Universal Common Ancestor of modern cells (LUCA). Several viral lineages originated independently by transformation of ribocells into virocells (cells producing virions). Viral genomes originated from ancestral chromosomes of ribocells and virions from micro-compartments, nucleoprotein complexes or membrane vesicles present in ancient ribocells. Notably, this updated version of the escape hypothesis suggests a working program to tackle the question of virus origin.”
Regressive hypothesis on the other hand suggests that viruses came about when some free-living ancestral cells lost their autonomy for some reason and adopted a parasitic life-style instead. Discovery of giant viruses rekindled the support for this hypothesis. Since giruses have large genomes unheard of in other types of viruses so far and are capable of more complex processes, some scientists have suggested that they might be descendants of more complex ancestors.
#Abrahão et al., The analysis of translation-related gene set boosts debates around origin and evolution of mimiviruses, 2017.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313130/
Quote: ”Since the discovery of mimiviruses, many theories regarding their origin and evolutionary history have arisen. As soon as the first mimivirus was discovered and its genome analyzed, authors began to hypothesize that this virus stands within the tree (or rhizome [60]) of life [4]. In the following years, the discovery of new giant viruses increased their known pangenome, which supported the initial theories and opened windows for new ones by suggesting that they originated from a fourth TRUC of life [34,50] and also that they probably coexisted with cellular ancestors, evolving mainly through a genome reductive pattern [30,31].”
As opposed to the two above, the third hypothesis postulates that the viruses predate cellular life or coevolved with it. It capitalizes on the diversity of the viral genomes (all combinations of single-stranded/double-stranded RNA/DNA) and emphasizes the stark contrast to the uniformity seen in genomes of cellular organisms. Therefore, viruses descending from a precellular phase is the most plausible scenario.
#Koonin E. V., On the Origin of Cells and Viruses Primordial Virus World Scenario, 2009
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380365/pdf/NYAS-1178-47.pdf
Quote: “The concept of a precellular stage of biological evolution outlined here posits that the precellular stage of life’s evolution took place within networks of inorganic compartments that hosted a diverse mix of virus-like genetic elements.45,59 It is further proposed that these ensembles of genetic elements were the ancestral state from which cells emerged, probably, in multiple, independent escapes only two or three of which (the ancestors of bacteria and archaea, and possibly, eukarya) yielded stable cellular lineages that enjoyed a long-term evolutionary success. Considering this hypothetical consortial state of primordial life forms that eventually gave rise to cells, it seems reasonable to replace the acronym LUCA with LUCAS, for the Last Universal Common Ancestral State.”
There are many more publications in support of these three hypotheses above and other scenarios as well. It is not possible to cover all of them here, so the collection of references above are obviously not exhaustive.
– The current thinking is that viruses probably emerged multiple times from different origins, but we simply don’t know for sure yet.
All explanations we summarized above are still hypotheses though. Scientists still do not have a certain explanation through which mechanism viruses popped up in the game of life. Also, it does not mean that one single hypothesis is the correct one. Given the wide variety of viruses, scientists have converged on the idea that different types of viruses came about through different mechanisms at different points in time.
#Mart Krupovic, Valerian V. Dolja and Eugene V. Koonin. Origin of viruses: primordial replicators recruiting capsids from hosts. Nature Reviews Microbiology, 2019.
https://www.nature.com/articles/s41579-019-0205-6
Quote: “Here, we outline a ‘chimeric’ scenario under which different types of primordial, selfish replicons gave rise to viruses by recruiting host proteins for virion formation. We also propose that new groups of viruses have repeatedly emerged at all stages of the evolution of life, often through the displacement of ancestral structural and genome replication genes.”
– And yet viruses are the most successful beings on this planet. There’s an estimated 10,000 billion, billion, billion viruses on earth.
Number of virus particles are estimated to be around 10^31:
#A. R. Mushegian. Are There 1031 Virus Particles on Earth, or More, or Fewer?, 2020.
https://jb.asm.org/content/202/9/e00052-20
Quote: “To summarize this very brief review of the history of a notion that, in my opinion, deserves to be called the Hendrix product or the Hendrix number, the current best estimate of the total number of virus-like particles on Earth remains close to 1031. When included in the scientific texts, it would be appropriate to credit this estimate to Hendrix et al. (1) or perhaps Hendrix et al. and Bar-On et al. (1, 18) to reflect its persistence in the light of the new data.”
– If we put them all next to each other they would stretch for 100 million light years – 500 milky way galaxies wide.
If we take an average virus diameter of 100 nanometer (10^-7 m) – as of diameter of SARS-CoV-2 virus for instance– they would stretch 10^31 times 10^-7 m in total, which is equal to 10^24m = 105,700,083 light years!
# Bar-On et al., SARS-CoV-2 (COVID-19) by the numbers, 2020.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224694/
Quote: “SARS-CoV-2 is an enveloped virus ≈0.1 μm in diameter”
Assuming that the Milky Way has a diameter of 200,000 light-years, therefore 105,700,083 / 200,000 ≈ 500 Milky Way galaxies.
#López-Corredoira et al., Disk stars in the Milky Way detected beyond 25 kpc from its center, 2018.
https://www.aanda.org/articles/aa/abs/2018/04/aa32880-18/aa32880-18.html
Quote: “Our analysis reveals the presence of disk stars at R > 26 kpc (99.7% C.L.) and even at R > 31 kpc (95.4% C.L.).”
– Very recently, viruses became even weirder, when scientists found a completely new type. Giant viruses, nicknamed “girus”. Not only did it break all sorts of records but put to question many assumptions we had about their nature.
The first girus was identified in 2003. More on that below but for now a recent review on the topic would work to get warmed up to the topic.
#Brandes and Linial, Giant Viruses—Big Surprises, 2019.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563228/#B17-viruses-11-00404
Quote: “The first giant virus, Acanthamoeba polyphaga mimivirus (APMV), was discovered in 2003 [17]. Its size was unprecedented, being on the scale of small bacteria or archaea cells [18]. Unlike any previously identified virus, APMV could be seen with a light microscope [19,20]. Initially it was mistaken for a bacterium and recognized as a virus only ten years after its isolation [21]. Up to this day, most of its proteins remain uncharacterized [22,23]. Notably, even more than a decade after the discovery of APMV, the identification of giant viruses still sometimes involves confusion, as illustrated in the discovery of the Pandoravirus inopinatum [24], which was initially described as an endoparasitic organism, and Pithovirus sibericum [25], which was also misinterpreted as an archaeal endosymbiont (see discussion in References [21,26]).”
– Giruses even come with their own parasites, Virophages. Viruses that hunt other viruses, which seemingly makes no sense at all.
Virophages were first described in 2008 with the discovery of Sputnik within Acanthamoeba castellanii mamavirus. Scientists were surprised to see how the smaller virus, Sputnik, is able to hijack the viral factory and obstruct the replication of mamavirus. (More on this later) Since then several more virophages have been discovered associated with various other giant viruses.
#Bekliz et al., The Expanding Family of Virophages, 2016.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127031/
Quote: “Virophages replicate with giant viruses in the same eukaryotic cells. They are a major component of the specific mobilome of mimiviruses. Since their discovery in 2008, five other representatives have been isolated, 18 new genomes have been described, two of which being nearly completely sequenced, and they have been classified in a new viral family, Lavidaviridae. Virophages are small viruses with approximately 35–74 nm large icosahedral capsids and 17–29 kbp large double-stranded DNA genomes with 16–34 genes, among which a very small set is shared with giant viruses. ”
– And since we identified the first one in 2003, it seems like these giants are everywhere we look and are even weirder than we thought. In the oceans, in water towers, in the guts of pigs and the mouths of humans.
The first giant virus to be discovered was Acanthamoeba polyphaga mimivirus (APMV). Scientists isolated it from a sample collected from a water tower in the UK. Acanthamoeba polyphaga was the name of the amoeba within which these 400 nm big viruses were identified. Since they were previously mistaken for small gram-positive bacteria, they were named Mimivirus for mimicking microbe. Until their discovery, viruses were characterised by a particle size smaller than 200 nm, which is partly the reason scientists have missed them until then – they have just filtered them out when experimenting with virus samples.
#La Scola et al., A Giant Virus in Amoebae, 2003.
Sequences of several giant virus genomes, such as of Mimiviridae, Mamaviridae, Marseilleviridae, have also been identified in human gut microbiota:
#Scarpellini et al., The human gut microbiota and virome: Potential therapeutic implications, 2015.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185617/
Quote: “In the past decades microbiological investigations have further discovered viruses infecting human intestinal parasites such as amebae (e.g. Mimiviridae, Mamaviridae, Marseilleviridae) from cooling towers, rivers, lakes, and seawater. These viruses are defined “giant” because of their dimensions. They are DNA viruses and their existence has been frequently doubted because they are undetectable by small-pore filtration (Table 1). Some of the Mimiviruses have been associated with pneumonitis and diarrhoea in humans although evidence is controversial [19].”
#Popgeorgiev et al., Describing the silent human virome with an emphasis on giant viruses, 2013.
https://www.karger.com/Article/FullText/354561
Quote: “Moreover, several studies have identified the presence of giant viruses in the human gut in both adults and babies [16,19,134]. Breitbart et al. [19] detected sequences homologous to Lymphocystis disease virus (Iridoviridae), a fish-infecting pathogen, whereas Gordon et al. [16] detected previously uncharacterized Pox-related viral sequences in the infant gut.”
A megaphage called Lak has also been found in guts of baboons, humans and pigs:
#Devoto et al, Megaphages infect Prevotella and variants are widespread in gut microbiomes, 2019.
https://www.nature.com/articles/s41564-018-0338-9
Quote: “We investigated the gut microbiomes of humans from Bangladesh and Tanzania, two African baboon social groups and Danish pigs; many of these microbiomes contain phages belonging to a clade with genomes >540 kilobases in length, the largest yet reported in the human microbiome and close to the maximum size ever reported for phages. We refer to these as Lak phages.”
A year later researchers collected samples from various ecosystems, from human and other animal microbiomes to oceans, lakes, sediments, soils and found hundreds of different megaphage genomes:
#Al-Shayeb et al., Clades of huge phages from across Earth’s ecosystems, 2020.
https://www.nature.com/articles/s41586-020-2007-4
– Giruses look funny, like hairy geometric forms or mini pickles – much larger than all viruses we knew which explains how they could hide in plain sight for centuries – scientists saw them under their microscopes and just thought they had to be bacteria.
Since the identification of the first one, over a hundred giruses have been discovered and classified across several families such as Mimiviridae, Pithoviridae, Pandoraviridae, Phycodnaviridae, under the phylum Nucleocytoviricota (or nucleocytoplasmic large DNA viruses (NCLDV)). Following image show 4 giruses in comparison to HIV and the bacterium E.Coli:
#New Scientist, Giant viruses may just be small viruses that stole hosts’ genes, 2017.
Following image shows electron micrographs of some giant viruses within their capsids.
#Colson et al., Giant Viruses of Amoebae: A Journey Through Innovative Research and Paradigm Changes, 2017.
https://www.annualreviews.org/doi/abs/10.1146/annurev-virology-101416-041816
Until the discovery of giant viruses, a typical virus filter was around 200 nm, meaning it was not expected to find a virus with a larger diameter than that. Partly due to this preconditioning, giruses went undetected for a long time.
#Wessner, D. R. Discovery of the Giant Mimivirus. Nature Education, 2010.
https://www.nature.com/scitable/topicpage/discovery-of-the-giant-mimivirus-14402410/
Quote: “First observed in 1992, Acanthamoeba polyphaga mimivirus (APMV) presents an interesting story of scientific inquiry. During the investigation of a pneumonia outbreak, researchers noticed particles resembling Gram-positive bacteria residing within amoebae isolated from a water-cooling tower. Because other bacterial species that cause pneumonia, like Legionella pneumophila, reside within amoebae (Rowbotham 1980), the investigators hypothesized that they had found another pneumonia-causing bacterium. Subsequent research, however, showed that they had identified not a bacterium, but a giant virus (La Scola et al. 2003).”
– Most giruses we found so far hunt amoeba and other single celled beings.
The following paper puts a sample of giant viruses together pulled from a complete genome database – satisfying the condition of “eukaryote-infecting viruses with at least 500 protein-coding genes”. Authors identified 19 eukaryote-infecting giant viruses and summarized them together with their host organisms in the following table.
#Brandes and Linial, Giant Viruses—Big Surprises, 2019.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563228/pdf/viruses-11-00404.pdf
– When they find a victim, they connect with it and use its natural processes to enter the cell. Like all viruses, their goal is to misappropriate the victims infrastructure and procreate.
#Brandes and Linial, Giant Viruses—Big Surprises, 2019.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563228/pdf/viruses-11-00404.pdf
Quote: “All amoebae-infecting giant viruses rely on the non-specific phagocytosis by the amoebae host [55]. Interestingly, a necessary condition for phagocytosis is a minimal particle size (~0.6 µm [58]), as amebae (and related protozoa) naturally feed on bacteria. It is likely that this minimal size for inducing phagocytosis has become an evolutionary driving force for giant viruses. This fact, together with the largely uncharacterized genomic content of giant viruses, may suggest that much of the content in the genomes of giant viruses serves only for volume filling to increase their physical size. Giant viruses share not only the cell entry process. When they exit the host cells during lysis, as many as 1000 virions are released from each lysed host via membrane fusion and active exocytosis [59], which are relatively rare exit mechanisms in viruses.”
– The girus unloads its attack proteins and genetic material and rearranges the cell from the inside. Its structural elements, protein production machinery and large amounts of mitochondria for energy are changed to become an actual factory called viroplasm.
#Colson et al, Mimivirus: leading the way in the discovery of giant viruses of amoebae, 2017.
https://www.nature.com/articles/nrmicro.2016.197/
Following image (a) is a schematic of the replication cycle of Acanthamoeba polyphaga mimivirus (APMV). In the first stage virus particles are seen at the surface of the amoeba. Then, the virus enters the cell through phagocytosis and releases its genome into the cytoplasm. This seeds the virus factory and groups of virus particles can be detected around the virus factory ~8h onwards. Around 12h after infection, amoebal lysis occurs, i.e. they rupture the host cell. Through b-e, electron microscopy images APMV particles and Acanthamoeba sp. cells are shown in corresponding stages along the replication cycle.
Panel b) A mimivirus particle
Panel c) A mimivirus factory in the amoeba cytoplasm, 8 h post-infection.
Panel d) The edge and periphery of a virus factory. This is where several steps of virus production take place such as internal membrane production and assembly, capsid assembly and DNA packaging, and fibre acquisition, 8 h post-infection.
Panel e) An Acanthamoeba sp. amoeba with the cytoplasm filled with mimivirus particles, ∼12 h post-infection.
– Some giruses even construct a membrane to shield it from the cell's antiviral defenses.
Viroplasms, or viral factories, are not exclusive to giruses – many viruses are observed to form them once they infect the host cell. They are inclusions in the cytoplasm of the host cell where the virus material gets aggregated and viral replication takes place. Though it is not directly shown that giruses use this as a defense mechanism against the host's processes, it is the most likely explanation. It might also be used in the replication cycle to organize the viral factory since the newly produced viruses bud from this region.
#Chelkha et al., Host–virus interactions and defense mechanisms for giant viruses, 2020.
https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/nyas.14469
Quote: “Their replication occurs in viral factories, which were also described for other viruses, including DNA viruses (herpesviruses) and RNA viruses (such as flaviviruses or coronaviruses).”
Following study shows the different stages of assembly in the viral factory:
#Mutsafi et al., Membrane Assembly during the Infection Cycle of the Giant Mimivirus, 2013.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003367
– Once finished, the viroplasm begins to assemble new giruses, using the victim up from the inside until it is filled up. Finally the invader usually orders the cell to self-destruct and releases new giruses to look for new prey.
As represented in the schematic above, once the viral factory is set, the production line of new viruses Not all viruses assemble the new members in the exact same way. Some manufacture one type of viral ‘body part’ at a given time and go step by step whereas some others get down to fabricating everything all at once.
#Colson et al., Giant Viruses of Amoebae: A Journey Through Innovative Research and Paradigm Changes, 2017.
https://www.annualreviews.org/doi/abs/10.1146/annurev-virology-101416-041816
Quote: “The virion assembly step also differs among giant viruses. In the case of mimiviruses, virion internal membrane biogenesis and assembly, capsid assembly, DNA packaging, and fiber layer assembly occur successively from the inside to the outside of the virus factory. For pandoraviruses, pithoviruses, and Mollivirus sibericum, the envelope and interior of the virion are assembled simultaneously (97). The release of neosynthesized giant viruses occurs through amoebal lysis in all cases except for Mollivirus sibericum, for which this event seems to involve exocytosis without cell lysis. It is worth noting that the virus factory, which is a replication organelle where viral and cellular components are recruited, was assimilated to the nucleus of a cell infected by viruses, itself called the virocell (29).”
Following electron micrographs of the amoeba Acanthamoeba castellanii infected with mimivirus (panel a) shows how viral factories look like in the cytoplasm of the host (panel c).
– But what makes giruses special is not their modus operandi or their size even. It is that they are much more complex than thought possible for a virus.
#Schulz et al., Giant viruses with an expanded complement of translation system components, 2017.
https://science.sciencemag.org/content/356/6333/82
Quote: “Our results rather imply piecemeal capture of eukaryotic translation machinery components and are most compatible with independent origins of giant viruses from much smaller viruses (17, 19). Although the biological underpinning of the high content of translation-related genes in Klosneuviruses is uncertain, the hosts of these viruses might be particularly efficient in shutting down translation upon virus infection, thus rendering virus-encoded translation system components essential for viral reproduction.”
#Colson et al., Giant Viruses of Amoebae: A Journey Through Innovative Research and Paradigm Changes, 2017.
https://www.annualreviews.org/doi/abs/10.1146/annurev-virology-101416-041816
Quote: “Moreover, giant viruses of amoebae are complex microorganisms in terms of their genomic and protein contents. Their genomes harbor between 444 and 2,544 predicted genes, including many that are absent from any other viral genomes, and encode translation components.”
– Your cells have around 20,000 genes.
Human genome has around 20,000 protein coding genes, though it is still an open question.
GENCODE and RefSef, which are two genome databases, give the number of protein encoding genes as 19,951 and 19,531 respectively. Find the numbers in the following pages:
#Statistics about the current GENCODE Release (version 37)
https://www.gencodegenes.org/human/stats.html
#NCBI Homo sapiens Updated Annotation Release 109.20210226
https://www.ncbi.nlm.nih.gov/genome/annotation_euk/Homo_sapiens/109.20210226/
An article addressing the issue with varying number of genes in human genome:
#Cassandra Willyard. New human gene tally reignites debate. Nature News. 2018.
https://www.nature.com/articles/d41586-018-05462-w
Quote: “In 2000, with the genomics community abuzz over the question of how many human genes would be found, Ewan Birney launched the GeneSweep contest. Birney, now co-director of the European Bioinformatics Institute (EBI) in Hinxton, UK, took the first bets at a bar during an annual genetics meeting, and the contest eventually attracted more than 1,000 entries and a US$3,000 jackpot. Bets on the number of genes ranged from more than 312,000 to just under 26,000, with an average of around 40,000. These days, the span of estimates has shrunk — with most now between 19,000 and 22,000 — but there is still disagreement (See 'Gene Tally').”
– A typical bacterium has a few thousand genes.
#Land et al., Insights from 20 years of bacterial genome sequencing, 2015.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361730/pdf/10142_2015_Article_433.pdf
Quote: “Although a typical bacterial genome is around 5 million bp and encodes about 5000 proteins, the range of sizes is quite broad—more than a hundredfold. The largest genome currently (January 2014) that is complete and in GenBank is Sorangium cellulosum strain So0157-2, at 14,782,125 bp, and contains 11,599 genes (Han et al. 2013). The smallest bacterial genome sequenced is Candidatus Nasuia deltocephalinicola strain NAS-ALF; the genome encodes a mere 137 proteins, and is only 112,091 bp in length (Bennett and Moran 2013).”
– The Coronavirus has around 15, HIV or the flu around 10.
Coronavirus has around 15 genes, each colored section corresponds to a gene of the reference sequence of SARS-CoV-2 (hCoV-19/Wuhan/WIV04/2019).The following database provides and helps visualize the information on the genome, proteins, mutations, etc.
#GISAID, Genomic epidemiology of novel coronavirus - Global subsampling, 2021
https://www.gisaid.org/epiflu-applications/hcov-19-reference-sequence/
#Li et al. An integrated map of HIV genome-wide variation from a population perspective. 2015.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358901/
Quote: “The HIV genome contains nine genes that encode fifteen viral proteins”
#Clancy, S. Genetics of the influenza virus. 2008.
https://www.nature.com/scitable/topicpage/genetics-of-the-influenza-virus-716/
Quote: “With the HA and NA genes, the influenza A genome contains eight genes encoding 11 proteins.”
– The number of genes alone is certainly not everything, the tomato for example has 35,000 genes.
#The Tomato Genome Consortium. The tomato genome sequence provides insights into fleshy fruit evolution. Nature. 2012.
https://www.nature.com/articles/nature11119/
Quote: “The pipeline used to annotate the tomato and potato8 genomes is described in Supplementary Information section 2. It predicted 34,727 and 35,004 protein-coding genes, respectively.”
– But generally we think of life as a complex system, so below a certain complexity level, something may be closer to dead material rather than a living organism. But giruses can have hundreds or even thousands of genes, blurring the line between living and dead things.
When scientists first sequenced 1,181,404 base pairs genome of Mimivirus in 2004, shortly after its discovery, they found unique genes as well as core genes seen in other families in the same phylum, nucleocytoplasmic large DNA viruses (NCLDV). The new genes they found were implying functions in protein translation, protein folding and DNA repair. Moreover, they identified seven mimivirus proteins that are related to eukaryotic counterparts. Based on this, authors suggest to include Mimivirus as a distinct branch in the tree of life. However, this view is challenged by the other scientists in light of viruses' abilities to acquire genes from their host.
#Raoult et al, The 1.2-megabase genome sequence of Mimivirus, 2004.
https://pubmed.ncbi.nlm.nih.gov/15486256/
Since then many other giruses have been discovered and sequenced giving way to large scale genomic studies.
Following chart shows the genome sizes of some giant viruses of amoeba in comparison to their sizes.
#Colson et al., Giant Viruses of Amoebae: A Journey Through Innovative Research and Paradigm Changes, 2017.
https://www.annualreviews.org/doi/abs/10.1146/annurev-virology-101416-041816
Quote: “The large gene armamentarium of giant viruses of amoebae, and particularly the presence of genes involved in the transcription and translation apparatus, suggests relative independence of these viruses from their hosts with regard to replication. However, different patterns exist for different giant viruses. Notably, pandoraviruses, Mollivirus sibericum, and the marseillevirus Noumeavirus were described to be devoid of transcription-associated proteins, and it has been suggested that this conditions the implication of the amoebal nucleus in viral replication (97, 98).”
– And it is not just the numbers that are special, but also what these genes do. We used to think of viral genes as the simplest of instructions, just enough to overcome the defense of their victims and make new viruses. But many girus genes are completely unique, basically mystery genes.
#Colson et al., Giant Viruses of Amoebae: A Journey Through Innovative Research and Paradigm Changes, 2017.
https://www.annualreviews.org/doi/10.1146/annurev-virology-101416-041816
Quote: “Gene sequences transferred horizontally also represent a substantial proportion of Mimivirus genes, around 10% (9, 29), and include sequences found in bacteria, eukaryotes, archaea, and other viruses; estimates of their proportions vary according to differing analyses and interpreta- tions. Aside from their number, the sense of these transfers (i.e., whether Mimivirus is the donor or the acceptor) has been much debated for some genes (9, 29–32). The last major group of genes is the ORFans, which are genes without homologs in sequence databases. These genes, which represent new putative functions, accounted for almost one-half of the gene content of Mimivirus (48%). The proportion of these ORFans among the 114 proteins identified in the virion was in the same order of magnitude (40%) (33), which highlights the fact that many of the structural and functional components of Mimivirus remain unknown.”
#Legendre et al., mRNA deep sequencing reveals 75 new genes and a complex transcriptional landscape in Mimivirus, 2010.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860168/pdf/664.pdf
Quote: “Another main result of our study is the identification of 75 new genes not previously predicted by traditional bioinformatic analysis. About one half of these transcripts do not appear to encode a protein product, thus suggesting that ncRNAs, a handful of which have been described in other large DNA viruses (Sullivan 2008), may constitute a significant component of the gene expression regulatory network of Mimivirus. Following the correction of several sequence errors and the precise mapping of the intron–exon structure of two genes, the Mimivirus genome now exhibits 900 protein coding genes, six tRNA, and 75 ‘‘new’’ genes, for a total of 981 transcription units.”
– Even more confusing, a huge selection of their genes that are actually hallmarks of living things. Genes that regulate nutrient intake, energy production, light harvesting, replication or are just necessary to keep cells alive.
As more and more girus genomes are sequenced, scientists can also do phylogenetic studies. Following study analyzed the metabolic genes across 500 girus genomes and found genes related to nutrient uptake, light harvesting, and nitrogen metabolism as well as to parts of glycolysis and the TCA cycle. Following figure represents the distribution of genes across different functions.
#Mohammad Moniruzzaman, Carolina A. Martinez-Gutierrez, Alaina R. Weinheimer & Frank O. Aylward. Dynamic genome evolution and complex virocell metabolism of globally distributed giant viruses, Nature Communications, 2020,
https://www.nature.com/articles/s41467-020-15507-2
Quote: “In this study we assess the genomic diversity and encoded metabolic diversity of NCLDV in the environment through large-scale generation of metagenome-assembled genomes and analysis of their functional capacity. We identify diverse metabolic genes in widespread giant viruses, including many involved in nutrient uptake and processing, light harvesting, and central nitrogen metabolism, underscoring the complex interplay between these viruses and their hosts. In addition, we report numerous giant viruses that encode components of glycolysis, gluconeogenesis, the glyoxylate shunt, and the TCA cycle, including one genome with a 70%-complete glycolytic pathway, suggesting that they can re-program fundamental aspects of their host’s central carbon metabolism.”
– Some recent studies have even suggested that some giruses with very complex genomes may be able to maintain a basic level of metabolism on their own, which if true will shake up what we thought of viruses even more.
Recently, scientists have found similar sequences in the genome of a girus, Pandoravirus massiliensis, to those that code for proteins involved in energy metabolism. Authors interpreted this finding as evidence that viruses may carry out energy production. However, this line of research is still in its early days and many experiments await to prove that viruses can carry out rudimentary metabolic processes independently.
#Aherfi et al., Tricarboxylic acid cycle and proton gradient in Pandoravirus massiliensis: Is it still a virus?, 2020.
https://www.biorxiv.org/content/10.1101/2020.09.21.306415v1
Quote: “Herein, we investigated possible energy production in Pandoravirus massiliensis, the largest of our giant virus collection. [...] An attempt to identify enzymes involved in energy metabolism revealed that 8 predicted proteins of P. massiliensis exhibited low sequence identities with defined proteins involved in the universal tricarboxylic acid cycle (acetyl Co-A sy nthase; citrate synthase; aconitase; isocitrate dehydrogenase; α-ketoglutarate decarboxylase; succinate dehydrogenase; fumarase). [...] Our findings show for the first time that energy production can occur in viruses, namely, pandoraviruses, and the involved enzymes are related to tricarboxylic acid cycle enzymes.”
– We still don’t know anything for sure, but one idea about girus genes is that they might fundamentally alter the physiology and evolution of their victims, by integrating their own genomes and merging with them into chimeric organisms.
#Mohammad Moniruzzaman, Alaina R. Weinheimer, Carolina A. Martinez-Gutierrez & Frank O. Aylward. Widespread endogenization of giant viruses shapes genomes of green algae. Nature. 2020.
https://www.nature.com/articles/s41586-020-2924-2
Quote: “Bacteriophage integration into host genomes has long been recognized as a major driver of genomic innovation28; indeed, many key physiological adaptations of bacteria can be traced to prophage-encoded genes that confer unique capabilities to their hosts29. It has been traditionally thought that this mode of genome evolution is less common in eukaryotes 30,31, but our identification of widespread GEVEs in chlorophyte genomes potentially challenges this view. Examples in which large dsDNA viruses endogenize are largely restricted to a narrow range of viruses with specific infection strategies, such as the phaeovirus Ectocarpus siliculosus that can integrate into the genome of host gametes as part of replication cycles 32–34. The widespread endogenization of NCLDV into chlorophytes therefore represents an underappreciated aspect of eukaryotic genome evolution and suggests that many eukaryotic lineages have access to a much larger array of genomic material than previously thought.”
GEVEs: Giant Endogenous Viral Elements
NCLDV: Nucleocytoplasmic large DNA viruses
– Or the other way around, take some host genes with them and be changed themselves. For billions of years giruses may have been existing alongside and infecting cells, exerting an unseen influence on the development of life. Not just as a parasite, but jerking evolution in different directions by mixing genes around in all directions.
#Albert J Erives, Phylogenetic analysis of the core histone doublet and DNA topo II genes of Marseilleviridae: evidence of proto-eukaryotic provenance, 2017.
https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-017-0162-0
Quote: “Altogether, these findings and other recent results raise additional questions. For example, could the evolution of some large viral genomes have led to core histones functioning in compaction of viral DNA into capsids within its giant replication factories [48], and/or protection of viral DNA from prokaryotic endonucleases? In support of the latter, it is noteworthy that the prokaryotic CRISPR system, which is a dsDNA endonuclease-based anti-viral mechanism in ~ 90% of Archaea and ~ 40% of Bacteria [49, 50], is impeded by the eukaryotic nucleosome [51].”
– The virophage Sputnik is hunting a girus called Mamavirus that itself is hunting amoebae.
Sputnik was first described in 2008 partly by the same group of scientists who identified the first giant virus, Acanthamoeba polyphaga mimivirus (APMV), in 2003. In the following study, they have identified another strain of APMV which they called Mamavirus – because it looked even bigger than the first giant virus, Mimivirus. They found that mamavirus, similarly to mimivirus, forms a giant viral factory and has a multilayered membrane covered with fibrils. Even more surprisingly, they observed some smaller viral particles, ~50 nm,
in virus factories and in the cytoplasm of the infected cells. They named this new virus within mamavirus, Sputnik – due to its close relation to the bigger virus.
# La Scola et al. The virophage as a unique parasite of the giant mimivirus. 2008.
https://www.nature.com/articles/nature07218
Quote: “Here we describe an icosahedral small virus, Sputnik, 50 nm in size, found associated with a new strain of APMV. Sputnik cannot multiply in Acanthamoeba castellanii but grows rapidly, after an eclipse phase, in the giant virus factory found in amoebae co-infected with APMV4. Sputnik growth is deleterious to APMV and results in the production of abortive forms and abnormal capsid assembly of the host virus.”
Two years later, the cryo-electron microscopy (cryoEM) three-dimensional (3D) reconstruction of Sputnik is published:
#Sun et al., Structural Studies of the Sputnik Virophage, 2010.
– Sputnik is a tiny, minimalistic virus that does not even have the genes and tools to replicate itself. What it does have, is the ability to hijack the viroplasm factories of mamaviruses.
Scientists observed that Sputnik was produced in the same viral factories as mamavirus but with different kinetics and at different specific locations. It was not able to multiply on its own and was also produced earlier than mamavirus. Compared to the 1200 kb genome captured in the ~400nm capsid of its host APMV, Sputnik comes as tiny with an 18 kb genome within a diameter of 50nm. Scientists predicted 21 genes from its genome which encode for major and minor capsid proteins and proteins involved in DNA replication.
# La Scola et al. The virophage as a unique parasite of the giant mimivirus. 2008.
https://www.nature.com/articles/nature07218
Quote: “Sputnik has an 18,343-base-pair (bp) circular double-stranded DNA genome, with 21 predicted protein-coding genes ranging in size from 88 to 779 amino-acid residues.”
Quote: ”Sputnik did not multiply when inoculated into A. castellanii. However, this virus did grow, as demonstrated by transmission electron microscopy and polymerase chain reaction, in A. castellanii coinfected with mimivirus or mamavirus”
#Desnues et al., Sputnik, a Virophage Infecting the Viral Domain of Life, 2012.
https://www.sciencedirect.com/science/article/pii/B9780123946218000133?via%3Dihub
Quote: “B. Virophage hijacking of the viral factory
Immunofluorescence analysis using mouse anti-Sputnik antibodies allowed the detection of Sputnik particles inside amoebas at T0, corresponding to 30min p.i. The colocalization of Sputnik and Mimivirus signals further confirms the hypothesis that the two viruses share the same endocytic vacuoles. The mechanism by which Sputnik releases its genome into the cytoplasm of the amoeba is currently unknown but likely thrives on Mimivirus genome delivery. ”
– So virophages need their victim, the girus, to infect their victim, an amoebae, first, and then they can parasitize it.
Since the discovery of Sputnik, other virophages have also been shown to be involved in similar relationships to their host giant virus and the host of the giant virus itself.
Following is a recent review on virophages explaining interactions of various virophages with their hosts :
#Mougari et al., Virophages of Giant Viruses: An Update at Eleven, 2019.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723459/
Quote: “Virophages are defined as bona fide parasites of giant viruses. Therefore, they are deemed to depend on the transcription and DNA replication machinery of their so-called virus hosts, rather than on that of the cell host.”
– A mamavirus viroplasm infected by sputnik can only produce very few new giruses and among these, many are deformed and broken, unable to infect further cells. Instead it makes loads of new sputnik virophages.
Scientists observed that Sputnik causes around 70% less infective mamavirus particles and also decreased amoeba death. Also, mamavirus virions are observed to have thicker capsid layers when co-infected with Sputnik.
# La Scola et al. The virophage as a unique parasite of the giant mimivirus. 2008.
https://www.nature.com/articles/nature07218
Quote: “Only a small fraction of the mamavirus particles encapsidated Sputnik virions. However, coinoculation of mamavirus with Sputnik resulted in a roughly 70% decrease in the yield of infective mamavirus particles and a threefold decrease in amoeba lysis at 24 h. These findings showed that Sputnik is a parasite of mamavirus that substantially affects the reproduction of the host virus.”
Quote: “Sputnik co-infection was associated with a significant increase in the formation of abnormal mamavirus virions, characterized by partial thickening of the capsid (11% rather than 1%, P 5 0.0029). In the regular mamavirus virions, the capsid layer was 40 nm thick; in contrast, in the presence of Sputnik, the thickness of the capsid wall could reach 240 nm (Fig. 1). In most cases, several capsid layers accumulated asymmetrically at one pole of the viral particle. Some of these abnormal particles seemed to be mature and to harbour fibrils only on the normal part of the capsid.”
– Other virophages are even more subtle. When they infect a viroplasm, they just integrate their genetic code into the newly produced giruses, like sleeper agents. The next time one of these infiltrated giruses successfully infects a cell it produces mostly virophages instead of giruses.
There is currently no direct evidence of an integrated virophage getting activated at a later stage in the giant virus life cycle. However, this is a likely scenario based on what is currently known.
#Desnues et al., Provirophages and transpovirons as the diverse mobilome of giant viruses, 2012.
https://pubmed.ncbi.nlm.nih.gov/23071316/
Quote: “Here we report the simultaneous discovery of a giant virus of Acanthamoeba polyphaga (Lentille virus) that contains an integrated genome of a virophage (Sputnik 2), and a member of a previously unknown class of mobile genetic elements, the transpovirons. The transpovirons are linear DNA elements of ∼7 kb that encompass six to eight protein-coding genes, two of which are homologous to virophage genes. Fluorescence in situ hybridization showed that the free form of the transpoviron replicates within the giant virus factory and accumulates in high copy numbers inside giant virus particles, Sputnik 2 particles, and amoeba cytoplasm. Analysis of deep-sequencing data showed that the virophage and the transpoviron can integrate in nearly any place in the chromosome of the giant virus host and that, although less frequently, the transpoviron can also be linked to the virophage chromosome ”
– Giruses are not completely defenseless though – a few years ago the world was in awe when scientists discovered CRISPR, a bacteria defense system against viruses. It turns out some giruses have a system that might be similar – a sort of girus immune system against virophages!
Details of the CRISPR mechanism and its applications would not be possible to cover here and probably deserve another video. In short, bacteria can integrate copies of viral genome bits into its own genome and use the information in those sequences next time it is attacked by the same type of virus.
Following is a review explaining CRISPR in the context of bacterial and archeal immunity:
#Sorek et al., CRISPR-Mediated Adaptive Immune Systems in Bacteria and Archaea, 2013
https://www.annualreviews.org/doi/full/10.1146/annurev-biochem-072911-172315
Scientist discovered a mechanism in mimivirus which might resemble CRISPR:
#Levasseur et al., MIMIVIRE is a defence system in mimivirus that confers resistance to virophage, 2016.
https://www.nature.com/articles/nature17146
Quote: “We hypothesized that mimiviruses harbour a defence mechanism resembling the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas system that is widely present in bacteria and archaea. ”
– In turn virophages can also be used as an anti girus defense mechanism by living cells. Some protists have been found that integrated the genetic code of virophages into their genome and kept them around. When they were infected by giruses, they released the virophages to destroy and take over the girus factories. In the end, the protist would still be killed by the girus infection, but instead of releasing giruses to kill its buddies, it released virophages to hunt them.
Scientists found virophage genomes integrated into hosts before: for example marine alga Bigelowiella natans contains virophages genomes. However, the first direct evidence of a virophage integrating its DNA into the genome of a cellular host comes from the relationship between marine protozoan Cafeteria roenbergensis, giant Cafeteria roenbergensis virus (CroV) and its virophage, mavirus. When scientists coinfected Cafeteria roenbergensis with CroV and mavirus, they observed that approximately one-third of the protists’ cells has taken up chunks of mavirus genome. Mavirus is able to do this thanks to a specific group of enzymes called integrases which enable DNA insertion into a host genome. Scientists found 11 copies of the mavirus genome scattered along the genome of Cafeteria roenbergens. However, these are not readily expressed genes, they can get activated only when the protozoan is infected with CroV – probably via a transcription factor produced by CroV. Only then, production of virophage particles is induced. Unfortunately, this does not directly protect the host cell. It still dies and spills CroV and virophage particles around. However, the released infectious mavirus particles inhibit CroV and protects other Cafeteria roenbergensis cells around. In light of this, scientists hypothesized that this mechanism might be serving as an antiviral defense system for the host cell collectively as a species.
#Fischer and Hackl , Host genome integration and giant virus-induced reactivation of the virophage mavirus, 2016.
https://www.nature.com/articles/nature20593
Quote: “We find that provirophage-carrying cells are not directly protected from CroV; however, lysis of these cells releases infectious mavirus particles that are then able to suppress CroV replication and enhance host survival during subsequent rounds of infection. The microbial host–parasite interaction described here involves an altruistic aspect and suggests that giant-virus-induced activation of provirophages might be ecologically relevant in natural protist populations.“
Following figure from the paper illustrates the mechanism works step by step:
Following review explores these type of defense mechanisms further:
#Koonin et al., Evolutionary entanglement of mobile genetic elements and host defence systems: guns for hire, 2019.
https://www.nature.com/articles/s41576-019-0172-9
– The amazing thing about everything we told you in this video is that we are still very much at the beginning. It has not even been twenty years since the discovery of giruses and virophages.
Since the discovery of the giant viruses, new and exciting research has been coming in. However, there are still many discoveries ahead. Mechanisms through which giant viruses interact with their hosts and virophages, giruses’ ecological roles within the wide range of environments that they are found, their genetic profiles and other potential hosts are only a few areas awaiting discoveries in the near future.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830010/#CR76
Quote: “Giant virus characterization studies have revealed a potential of future surprises in giant virus–host interactions. Evidence of this potential is that giant viruses have been found in diverse and unexplored environments, where they may be interacting with more organisms than we can imagine [14, 29, 92, 93]. Sequences of several giant viruses were found in human microbiome, but nothing is known about their interaction profile and ecological roles [94, 95]. Furthermore, it has been found that these viruses can encode genes that act on complex biochemical pathways [96–98]. ”