Viruses are the most abundant biological entities in the biosphere (Baltimore, 1971; Suttle, 2005; Suttle, 2007) and have been the subject of persistent debates as to their place in the domains of life. Active energy metabolism pathways and the autonomous ability to reproduce independently are the most fundamental criteria associated with living cells and therefore distinguish the three domains of life – archaea, bacteria, and eukarya – from viral entities. Specifically, the fundamental hallmark of all living organisms is the self-maintenance of their own functional and structural integrity via the biochemical transformations of environmental resources. (Dupré and O’Malley, 2009).

Viruses originally were defined as filterable agents capable of passing through membrane filters with pore sizes of 0.22 µm. Most viruses possess small genomes that carry only a handful of genes supporting their replication and capsid production in a host cell. Viruses have thus been characterized as ‘molecular genetic parasites’ that take advantage of cellular functions to replicate (Luria, 1959). Generally, once viruses find their replication site they hijack the host cellular metabolic pathways to their own advantage with the ultimate goal to replicate (Villarreal, 2005). However, ambiguity regarding the definition of viruses appears in the concept of a ‘virocell’, defined by Forterre, 2013 as a ‘living form’ of the virus, consisting of a living cell transformed to produce more virions (Forterre, 2013). At the blurred boundaries between viruses and cellular organisms, intracellular bacteria such as Rickettsia and Chlamydia also are known to hijack host energy metabolism enabling their persistence and proliferation (Driscoll et al., 2017; Gehre, 2015), a characteristic shared with viruses. Ultimately, however, viruses lack many of the essential attributes of living organisms, such as the ability to capture and store free energy, as well as autonomous replication and self-repairing capacity (Dupré and O’Malley, 2009; Regenmortel, 2010).

In 2003, the discovery of the giant viruses of amoeba revolutionized the view of viruses (La Scola et al., 2003). Specifically, the size of the giant virus particles (reaching up to 2.5 μm) and of their genome sizes (up to 2.5 Mb), encoding almost a thousand proteins, fundamentally changed the landscape of virus research (Philippe et al., 2013). Notably, Acanthamoeba polyphaga Mimivirus, the first giant virus of amoeba discovered, has a 1.2-Mbp genome, and possesses several genes encoding proteins involved in transcription and translation (Raoult et al., 2004; Raoult and Forterre, 2008b). Phylogenetic analyses have demonstrated that some bacterial and eukaryotic genes found in the Mimivirus genome, and other giant virus genomes, were acquired by horizontal gene transfer from amoebal hosts, and from amoebal bacteria parasites (Moreira and Brochier-Armanet, 2008), although most giant virus genes still have enigmatic origins.

Giant viruses represent a group of ancient viruses that are termed the Nucleo–Cytoplasmic Large DNA Viruses (NCLDVs). While some are found in amoebae, other of these viruses infect hosts ranging from algae to animals and form an apparently monophyletic group in the phylum Nucleocytoviricota (Colson et al., 2013). The giant viruses are classified into several families: Mimiviridae, Pithoviridae, Pandoraviridae, Phycodnaviridae, Poxviridae, Iridoviridae, Asfarviridae, and others. Many, including newly discovered viruses in the Mollivirus genus are not yet classified (Abergel et al., 2015; Legendre et al., 2014; Rolland et al., 2019).

The genomes of giant viruses encode proteins that had never before been identified in viruses. These proteins have sequence identity with closely related eukaryotic homologs (Chelkha et al., 2020; Sun et al., 2020). For example, Cafeteria roenbergensis virus, Klosneuviruses and Tupanviruses encode several gene products that are involved in protein translation (Abrahão et al., 2018; Schulz et al., 2017); the presence of such translation machinery had not been previously described in viruses. This finding suggested that those viruses may have relative independence from their hosts (and hence are ‘quasi-autonomous’ viruses) (Claverie and Abergel, 2010). This has led to a reconsidering of the historical parasitic hallmark of viruses (Abrahão et al., 2017; Raoult and Forterre, 2008a). In addition to the translation components, giant virus gene products have been implicated in RNA maturation, DNA maintenance, and proteostasis (Fischer et al., 2010; Yutin et al., 2013). Recently, defined metabolic genes involved in specialized cellular biochemical pathways have also been discovered in some giant viruses (Aherfi et al., 2022; Moniruzzaman et al., 2020; Schulz et al., 2020; Schvarcz and Steward, 2018). Herein, we analyze and describe giant virus genes encoding enzymes that are potentially involved in traditional biochemical pathways, findings that challenge the last distinguishing barriers separating the traditional domains of life and the giant viruses.

Carbohydrates are key enzymatic substrates for many essential metabolic pathways in cells (Maughan, 2009). Generally, autotrophic organisms biosynthesize carbohydrates from carbon dioxide and water, via photosynthesis (Butterworth, 2005; Lehninger et al., 2004; Nelson and Cox, 2017). All organisms then break down stored or consumed carbohydrates in order to produce energy for cell functioning (Nelson and Cox, 2017). Both autotrophic and heterotrophic organisms temporarily store their generated energy in the form of high-energy molecules, for example adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH), for use in the various metabolic processes (Sanders, 2016).

Although some viruses in the Nucleocytoviricota phylum infect known hosts such as amoeba, it is not clear if these are actually the specific hosts. In any case, auxiliary metabolic genes (AMG) encoded by giant viruses appear to exercise control and modulation of host cellular energetic metabolism, especially during viral genome replication, gene expression, and virion assembly (Sun et al., 2020). Such control mechanisms can be based on transcriptional regulation of nuclear and mitochondrion-encoded genes that are involved in energy metabolism, as observed with coccolithoviruses (Ku et al., 2020). Single cell transcriptomics of the microalga Emiliania huxleyi during infection by its specific giant virus showed that either host or viral transcriptome dominated the generated mRNA pool, and that only very few cells were observed in intermediate states. The rapid shutdown of host transcript generation indicates that the E. huxleyi coccolithovirus massively takes over controlling synthesis of almost the entire mRNA pool.

Many giant viral genes and gene products related to energy production and metabolic pathways have been identified recently (Aherfi et al., 2022; Ha et al., 2021; Moniruzzaman et al., 2020; Figure 1). In a detailed study examining a database of 2436 annotated Nucleocytoviricota, including metatranscriptomic data from California’s surface waters, hundreds of viruses, mainly from the Mimiviridae and Phycodnaviridae families, were identified. Many expressed viral transcripts in this dataset are genes involved in glycolysis (e.g. phosphofructokinase [EC 2.7.1.11], glyceraldehyde 3-phosphate dehydrogenase [EC 1.2. 1.12], phosphoglycerate mutase [EC 5.4.2.11]), gluconeogenesis (e.g. phosphoenolpyruvate carboxykinase [EC 4.1.1.32] and fructose-1,6-bisphosphatase [EC 3.1.3.11]), the tricarboxylic acid (TCA) cycle (e.g. succinate dehydrogenase [EC 1.3.5.1]), and the pentose phosphate pathway (e.g. 6-phosphogluconate dehydrogenase EC 1.1.1.1; Ha et al., 2021; Ha et al., 2021).

Figure 1

Download asset Open asset

Glycolysis and gluconeogenesis

Glycolysis is an ancient metabolic pathway that occurs in the cytoplasm of the cell and converts glucose into pyruvate, which is accompanied by transfer of electrons to NAD⁺ in order to generate NADH₂ (Potter and Fothergill-Gilmore, 1993; Kumari, 2018). Inversely, gluconeogenesis is a process occurring in animals, fungi, plants, and bacteria, which results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, amino acids, and glycerol (Rodwell et al., 2015).

A genomic study using environmental metagenome-assembled genomes (MAGs), identified genes encoding the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase, and phosphoglycerate kinase. These genes were considered to be particularly prevalent within the Mimiviridae (Figure 2A) and to a lesser extent in the Phycodnaviridae (Moniruzzaman et al., 2020). Studies of Mimivirus metagenomes identified a unique protein domain architecture, with a single fused gene encoding the enzymes glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase, which serve in two adjacent steps in glycolysis (Moniruzzaman et al., 2020). Such protein architecture is unique thus far and may reflect a more efficient process for enzymatic activity. Although this possibility requires experimental verification, it nevertheless highlights that giant viruses may drive evolutionary innovations of their metabolic genes.

Figure 2

Download asset Open asset

This same study revealed that three genes associated with gluconeogenesis were present in Mimiviridae genomes (Moniruzzaman et al., 2020): fructose 1,6-bisphosphatase, which catalyzes the biotransformation of fructose-1,6-bisphosphate into fructose-6-phosphate; phosphoenolpyruvate carboxykinase that converts oxaloacetate to phosphoenolpyruvate; and pyruvate carboxylase that catalyzes the carboxylation of pyruvate to form oxaloacetate (Figure 1, Table 1). The presence of such genes in infecting viruses also suggests there could be reprogramming of the host glycolysis pathways.

Table 1

Pathway	Enzyme	Function	KEGG*	Detected in	Family	Reference(s)
Amino acid catabolism	Glutamate dehydrogenase	Reversible conversion of glutamate to α-ketoglutarate and ammonia	R00243	Pandoravirus and others uncharacterized viruses†	Mimiviridae, Pandoraviridae and Phycodnaviridae	Moniruzzaman et al., 2020;  Aherfi et al., 2018
	Glutamine synthetase	Condensation of glutamate and ammonia to form glutamine:	R00253	Uncharacterized viruses†	Mimiviridae	Ha et al., 2021
	Glutaminase	Hydrolysis of glutamine into glutamate	R00256	Uncharacterized viruses†	Mimiviridae	Moniruzzaman et al., 2020; Ha et al., 2021
Lipide catabolism and β-Oxydation	Triacylglycerol lipase	Degrades triacylglycerol into glycerol and fatty acids	R01369	Prymnesium kappa virus RF01	Mimiviridae	Blanc-Mathieu et al., 2021
	Fatty-acyl-CoA Synthase	Conversion of a acetyl-CoA and seven malonyl-CoA molecules to produce a Palmitoyl-CoA	R05190	Prymnesium kappa virus RF01	Mimiviridae	Blanc-Mathieu et al., 2021
	CoA-transferase	Conversion acyl-CoA and acetate into fatty acid anion and acetyl-CoA.	R00393	Prymnesium kappa virus RF01	Mimiviridae	Blanc-Mathieu et al., 2021
	Acyl-CoA dehydrogenase	Desaturation of the acyl-CoA esters	R00392	Prymnesium kappa virus RF01 and others uncharacterized viruses†	Mimiviridae	Blanc-Mathieu et al., 2021
Citric Acid Cycle	Succinate dehydrogenase	Conversion of succinate into fumarate	R02164	Prymnesium kappa virus RF01, Pandoravirus massiliensis and others uncharacterized viruses†	Mimiviridae, Pandoraviridae and Phycodnaviridae	Moniruzzaman et al., 2020; Aherfi et al., 2022; Blanc-Mathieu et al., 2021; Ha et al., 2021;
	Citrate synthase	Claisen condensation between acetyl CoA and oxaloacetate to yield, after hydrolysis of the thioester bond, citrate and CoA	R00351	Pandoravirus massiliensis and others uncharacterized viruses†	Pandoraviridae and Mimiviridae	Aherfi et al., 2022; Moniruzzaman et al., 2020
	Aconitase	Catalyzes the stereospecific isomerization of citrate to isocitrate via cis-aconitate in a non-redox reaction	R01324	Pandoravirus massiliensis and others uncharacterized viruses†	Pandoraviridae and Mimiviridae	Moniruzzaman et al., 2020; Rodrigues et al., 2019; Aherfi et al., 2022
	Isocitrate/isopropyl malate dehydrogenase	Oxidative decarboxylation of isocitrate, resulting in alpha-ketoglutarate and carbon dioxide.	R00267 / R01652	Pandoravirus massiliensis and others uncharacterized viruses†	Pandoraviridae and Mimiviridae	Aherfi et al., 2022; Moniruzzaman et al., 2020
	Malate synthase	Conversion of enzyme are acetyl-CoA, H2O, and glyoxylate into (S)-malate and CoA.	R00472	Uncharacterized viruses†	Mimiviridae	Ha et al., 2021
	Alpha-ketoglutarate decarboxylase	Conversion of α-ketoglutarate to succinyl-CoA and produces NADH directly providing electrons for the respiratory chain	R00272	Pandoravirus massiliensis	Pandoraviridae	Aherfi et al., 2022
	Fumarase	Conversion of fumarate to L-malate	R01082	Pandoravirus massiliensis	Pandoraviridae	Aherfi et al., 2022
Fermentation	Pyruvate formate-lyase	Catalyzes the reaction of pyruvate +CoA acetyl-CoA +formate	R00212	Tetraselmis virus	Phycodnaviridae	Müller et al., 2012; Schvarcz and Steward, 2018; Sun et al., 2020
	Formate-lyase activating enzyme	Converts pyruvate and CoA into acetyl CoA and formate	R04710	Tetraselmis virus	Phycodnaviridae	Müller et al., 2012; Schvarcz and Steward, 2018
Gluconeogenesis	Fructose bisphosphatase	Converts fructose-1,6-bisphosphate to fructose 6-phosphate	R00762	Uncharacterized viruses†	Mimiviridae	Moniruzzaman et al., 2020; Ha et al., 2021
	Phosphoenolpyruvate carboxykinase	Converts oxaloacetate into phosphoenolpyruvate and carbon dioxide.	R00341	Uncharacterized viruses†	Mimiviridae	Moniruzzaman et al., 2020; Ha et al., 2021
	Pyruvate carboxylase	Catalyzes the conversion of pyruvate to oxaloacetate	R00344	Uncharacterized viruses†	Mimiviridae	Moniruzzaman et al., 2020
Glycolysis	Glyceraldehyde-3-phosphate dehydrogenase	Conversion of pyruvate to oxaloacetate	R01061	Uncharacterized viruses†	Mimiviridae and Phycodnaviridae	Moniruzzaman et al., 2020
	Phosphoglycerate mutase	Transfers the phosphate from 3-phosphoglyceric acid (3 PG) to the second carbon to form 2-phosphoglyceric acid (2 PG)	R01518	Uncharacterized viruses†	Mimiviridae and Phycodnaviridae	Moniruzzaman et al., 2020; Ha et al., 2021
	Phosphoglycerate kinase	Catalyzes the formation of ATP from ADP and 1,3-diphosphoglycerate	R01512	Uncharacterized viruses†	Mimiviridae and Phycodnaviridae	Moniruzzaman et al., 2020
Photosynthesis	Rhodopsin	Generating a proton motive force across the cell membrane (light dependent)	R02903	Organic Lake Phycodnavirus 2 and Phaeocystis globosa virus	Phycodnaviridae	Needham et al., 2019; Yutin and Koonin, 2012; Schulz et al., 2020
Mannitol metabolism	Mannitol 1-phosphate dehydrogenase	Converts D-mannitol 1-phosphate and NAD +into fructose 6-phosphate, NADH and H+.	R00758	Tetraselmis virus	Phycodnaviridae	Schvarcz and Steward, 2018
Saccharide degradation	Alpha-galactosidase	Catalyzes the removal of terminal α-galactose groups from substrates such as glycoproteins and glycolipids	R01101	Tetraselmis virus	Phycodnaviridae	Schvarcz and Steward, 2018

1. *

   KEGG codes for the biochemical reactions described (https://www.genome.jp/kegg/reaction/).

2. †

   Enzymes detected in NCLDVs from metagenome-assembled genome analysis.

Lipid metabolism consists of the catabolism of fatty acids and steroids/sterols in order to generate energy, and anabolic processes used to synthesize new lipids from smaller constituent molecules. Generally, lipids classified as fatty acids, triacylglycerols, phospholipids, sterols and sphingolipids are utilized in energy generation. Lipidomic β-oxidation is the main metabolic pathway for the degradation of fatty acid molecules to generate acetyl-CoA, which then enters in the TCA cycle.

A recent metatranscriptomic time-series study from the California Current surface waters has identified many novel transcripts putatively for lipid metabolism enzymes in viruses in the Nucleocytoviricota. Identified viral genes included those predicted to be involved in lipid β-oxidation (Ha et al., 2021). Genes encoding acyl-CoA dehydrogenases (EC 1.3.8.7), which catalyze the first committed enzymatic step of lipid β-oxidation, were consistently expressed across sampled timepoints, especially in the Mimiviridae. This finding again suggests that virus-mediated reprogramming of host central carbon metabolism is functional and occurs in oceanic surface waters (Ha et al., 2021).

In Prymnesium kappa virus RF01 (PCV RF01), numerous genes were found that are predicted to encode enzymes known to be involved in cellular lipid metabolism, such as a triacylglycerol lipase, which degrades triacylglycerol into glycerol and fatty acids (Figure 1, Table 1). These metabolites are used as precursors for ATP production via glycolysis and β-oxidation, respectively. In addition, it has been found that PCV RF01 encodes the key β-oxidation enzymes fatty acyl-CoA synthetase (EC 6.2.1.1), CoA-transferase (EC 2.8.3.8), and acyl-CoA dehydrogenase (EC 1.3.8.7) (Blanc-Mathieu et al., 2021). However, enzymes involved in the two intermediate steps immediately following each oxidation, enoyl-CoA hydratase (EC 4.2.1.17) or a β-ketothiolase (EC2.3.1.16), have not been detected in any giant virus to-date.

In cells, protein and/or amino acid utilization as a source of energy release mainly occurs when the intake of carbohydrates or lipids is insufficient to supply the required energy demand (Hothersall and Ahmed, 2013). In prokaryotes, and in mitochondria, glutamate dehydrogenase (EC 1.4.1.2) catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)+to NAD(P)H. The α-ketoglutarate is consumed by the TCA cycle to produce ATP (Glevarec et al., 2004; Miller and Magasanik, 1990; Plaitakis et al., 2017). MAGs studies of members of multiple NCLDV families report the presence of putative glutamate dehydrogenase, glutamine synthase (EC 6.3.1.2), and glutaminase (EC 3.5.1.2) enzymes (Moniruzzaman et al., 2020). Other analyses confirmed the presence of glutamate dehydrogenase in members of the Pandoraviridae family (Figure 1, Table 1; Aherfi et al., 2018; Hosokawa et al., 2021; Legendre et al., 2018; Philippe et al., 2013).

Glutaminase and glutamine synthase, two cellular enzymes that regulate primary energy metabolism, found in Mimiviridae were expressed upon infection (Ha et al., 2021). The glutaminase catalyzes the hydrolysis of glutamine into glutamate, regulating cellular energy metabolism via the increase of glutamate and α-ketoglutarate. This results in enhanced mitochondrial respiration and ATP generation (Campos-Sandoval et al., 2007; Hu et al., 2010). Glutamine synthetase plays a key role in the cellular utilization of carbon and nitrogen sources, helps modulate the energy budget in bacteria and mediates the release of energy stored in glutamine, that increases especially in stressed cells (Aldarini et al., 2017). Thus, the presence of such glutaminolysis enzymes in giant viruses may help reprogram metabolism by maximizing glutamine catabolism and thus increase available energy to promote virus replication and virion production (Ha et al., 2021).

In addition to primary metabolism energetic enzymes described above, a remarkable diversity of auxiliary metabolic genes involved in (i) carbon metabolism, nitrogen and nutrient cycling and (ii) soil organic matter degradation, have been found in marine viral communities (Table 2). It is hypothesized that these metabolic genes can complement deficient host metabolic pathways in order to sustain their host under environmental stressful conditions, with the overall goal to increase or maintain viral replication (Coutinho et al., 2017; Howard-Varona et al., 2020; Hurwitz and U’Ren, 2016). Such host / virus interactions appear to play an important role in the global ecosystem (Brum and Sullivan, 2015; Hurwitz and U’Ren, 2016; Suttle, 2007; Zimmerman et al., 2020).

Other gene products have been implicated in the reprograming of cellular physiology during giant virus infection, especially in nutrient processing and oxidative stress (Monier et al., 2017; Moniruzzaman et al., 2018; Sheyn et al., 2016). For example, it has been reported that Mimiviridae and Phycodnaviridae families exhibit superoxide dismutase and glutathione peroxidase activities encoded by crucial enzymes involved in oxidative stress regulation (Table 2). A superoxide dismutase encoding gene, involved in the breakdown of reactive oxygen species (ROS), was found encoded in the Megavirus chiliensis genome (Lartigue et al., 2015). These enzymes likely help to protect the viral replication machinery from damage by ROS generated during viral infection (Moniruzzaman et al., 2018; Moniruzzaman et al., 2020).

Sheyn et al., 2016. have shown that during lytic infection by Emiliana huxleyi virus, which infects the cosmopolitan unicellular eukaryotic algal host Emiliania huxleyi, glutathione was overproduced and that hydrogen peroxide (H₂O₂) was the major ROS during the onset of the lytic phase of infection. Moreover, the concomitant production of GSH and H₂O₂ occurred in the same cellular subpopulations that exhibited a higher rate of infection compared with cells that had little or no GSH and H₂O₂. Interestingly, the inhibition of ROS production significantly reduced virion production and inhibited host cell death (Sheyn et al., 2016).

Ostreococcus virus 6, a virus of the green alga Ostreococcus tauri, harbors a gene encoding an ammonium transporter that is expressed during viral infection. The activity of this protein may increase host NH4 +uptake rates to fulfill the increased nitrogen requirements of infected cells undergoing viral replication (Monier et al., 2017). Moreover, numerous genes that encode for phosphate, sulfur, magnesium and iron transporters, ferric reductases and multicopper oxidases were identified recently in several NCLDV clades (Moniruzzaman et al., 2020; Schulz et al., 2017). These genes may boost the acquisition of these essential nutrients for host cell metabolism during virion production, notably in marine environments where nutrient availability may be limiting for cellular growth (Behrenfeld and Kolber, 1999; Herbik et al., 2002; Hogle et al., 2018; Saikia et al., 2014).

In addition to enzymes implicated in carbohydrate metabolism for energy generation as described above, some giant virus genes also encode proteins involved in the biosynthesis and manipulation of carbohydrate, lipid, and nucleotide metabolism. Coccolithoviruses, belonging to the family Phycodnaviridae, possess a cluster of biosynthetic genes, including a serine palmitoyltransferase encoding gene, involved in the biosynthesis of glycosphingolipids, a major component of the virion membrane envelopes. High glycosphingolipid producing strains of E. huxleyi virus (EhV), which are extremely virulent and harbor a greater infectivity at high host densities, provide a selective advantage under laboratory conditions. However, field data obtained from natural environments suggest a better survival rate of slow glycosphingolipid producing EhVs, where lower host densities are encountered. Viral glycosphingolipid biosynthesis impacts on ecological balance in natural oceanic environments, where E. huxleyi plays an essential role in the global carbon cycle (Nissimov et al., 2019). Moreover, it has been shown that viral glycosphingolipids are able to suppress host cell growth by inducing programmed cell death (Monier et al., 2009; Rosenwasser et al., 2016; Vardi et al., 2009; Wilson et al., 2005).

Chloroviruses encode enzymes involved in (i) polysaccharide biosynthesis for example hyaluronan synthase, chitin synthase (Mohammed Ali et al., 2005). (b); (ii) sugar metabolism, for example GDP-D-mannose 4,6 dehydratase and GDP-4-keto-6-deoxy-D-mannose epimerase/reductase (Tonetti et al., 2003); and (iii) polysaccharides degradation, for example chitinase and 1–3-beta glucanase (Sun et al., 1999; Sun et al., 2000). These enzymes may be necessary for the infection cycle, for the ability to enter and exit the host cell (Van Etten et al., 2017). Polysaccharide lyases for example, pectate lyase, were also found to be encoded in the A. anophagefferens virus (AaV) genome (Moniruzzaman et al., 2014). It is probable that the genes encoding these putative enzymes were acquired by lateral gene transfer from either bacteria or from their host A. anophagefferens (Moniruzzaman et al., 2014). AaV genes encoding polysaccharide lyases have been mainly detected in ocean sampling throughout the world suggesting that these viruses play important role(s) in shaping the biogeochemical potential, in global marine system communities (Gann et al., 2020).

Analysis of the A. polyphaga Mimivirus genome revealed the presence of genes potentially involved in the biosynthesis of viosamine, which may have a role in the formation of the long fibers surrounding the virions (Piacente et al., 2012). Moreover, several giant viruses harbor the metabolic machinery that is involved in the production of glycoconjugate substrates (Fischer et al., 2010; Philippe et al., 2013; Piacente et al., 2015; Santini et al., 2013). Such genes include those encoding for nucleotide sugars enzymes and glycosyltransferases (Piacente et al., 2014). These viral enzymes may play structural role(s), which seems obvious when considering the highly glycosylated surface of the virions that protect them from the environment. They also may play a role in the phagocytic vacuole (Lairson et al., 2008; Legendre et al., 2014; Legendre et al., 2015; Piacente et al., 2014).

Finally, even steroid metabolism may be manipulated by NCLDV infection. Genomes of many mimiviruses and pandoraviruses contain cytochrome P450 genes, which encode P450 monooxygenase enzymes (Lamb et al., 2019). P450s are key enzymes in the metabolism of numerous endogenous regulatory molecules and xenobiotics in Bacteria, Archaea, and Eukarya. To support this suggestion, multiple genes involved in other aspects of steroid metabolism, notably steroid reductases, are also present and expressed (typically early) during the course of NCLDV infection (De Souza et al., 2021).

1. 1. Abergel C
   2. Legendre M
   3. Claverie JM

   (2015) The rapidly expanding universe of giant viruses: Mimivirus, Pandoravirus, Pithovirus and Mollivirus

   FEMS Microbiology Reviews 39:779–796.

   https://doi.org/10.1093/femsre/fuv037

   • PubMed
   • Google Scholar
2. 1. Abrahão JS
   2. Araújo R
   3. Colson P
   4. La Scola B

   (2017) The analysis of translation-related gene set boosts debates around origin and evolution of mimiviruses

   PLOS Genetics 13:e1006532.

   https://doi.org/10.1371/journal.pgen.1006532

   • PubMed
   • Google Scholar
3. 1. Abrahão J
   2. Silva L
   3. Silva LS
   4. Khalil JYB
   5. Rodrigues R
   6. Arantes T
   7. Assis F
   8. Boratto P
   9. Andrade M
   10. Kroon EG
   11. Ribeiro B
   12. Bergier I
   13. Seligmann H
   14. Ghigo E
   15. Colson P
   16. Levasseur A
   17. Kroemer G
   18. Raoult D
   19. La Scola B

   (2018) Tailed giant Tupanvirus possesses the most complete translational apparatus of the known virosphere

   Nature Communications 9:1–12.

   https://doi.org/10.1038/s41467-018-03168-1

   • PubMed
   • Google Scholar
4. 1. Aherfi S
   2. Andreani J
   3. Baptiste E
   4. Oumessoum A
   5. Dornas FP
   6. Andrade A
   7. Chabriere E
   8. Abrahao J
   9. Levasseur A
   10. Raoult D
   11. La Scola B
   12. 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

   • PubMed
   • Google Scholar
5. 1. Aherfi S
   2. Brahim Belhaouari D
   3. Pinault L
   4. Baudoin J-P
   5. Decloquement P
   6. Abrahao J
   7. Colson P
   8. Levasseur A
   9. Lamb DC
   10. Chabriere E
   11. Raoult D
   12. La Scola B

   (2022) Incomplete tricarboxylic acid cycle and proton gradient in Pandoravirus massiliensis: is it still a virus?

   The ISME Journal 16:695–704.

   https://doi.org/10.1038/s41396-021-01117-3

   • PubMed
   • Google Scholar
6. 1. Aldarini N
   2. Alhasawi AA
   3. Thomas SC
   4. Appanna VD

   (2017) The role of glutamine synthetase in energy production and glutamine metabolism during oxidative stress

   Antonie van Leeuwenhoek 110:629–639.

   https://doi.org/10.1007/s10482-017-0829-3

   • PubMed
   • Google Scholar
7. 1. Alperovitch-Lavy A
   2. Sharon I
   3. Rohwer F
   4. Aro E-M
   5. Glaser F
   6. Milo R
   7. Nelson N
   8. Béjà O

   (2011) Reconstructing a puzzle: existence of cyanophages containing both photosystem-I and photosystem-II gene suites inferred from oceanic metagenomic datasets

   Environmental Microbiology 13:24–32.

   https://doi.org/10.1111/j.1462-2920.2010.02304.x

   • PubMed
   • Google Scholar
8. 1. Anantharaman K
   2. Duhaime MB
   3. Breier JA
   4. Wendt KA
   5. Toner BM
   6. Dick GJ

   (2014) Sulfur oxidation genes in diverse deep-sea viruses

   Science (New York, N.Y.) 344:757–760.

   https://doi.org/10.1126/science.1252229

   • PubMed
   • Google Scholar
9. 1. Baltimore D

   (1971) Expression of animal virus genomes

   Bacteriological Reviews 35:235–241.

   https://doi.org/10.1128/br.35.3.235-241.1971

   • PubMed
   • Google Scholar
10. 1. Behrenfeld null
    2. Kolber null

    (1999) Widespread iron limitation of phytoplankton in the south pacific ocean

    Science (New York, N.Y.) 283:840–843.

    https://doi.org/10.1126/science.283.5403.840

    • PubMed
    • Google Scholar
11. 1. Béjà O
    2. Aravind L
    3. Koonin EV
    4. Suzuki MT
    5. Hadd A
    6. Nguyen LP
    7. Jovanovich SB
    8. Gates CM
    9. Feldman RA
    10. Spudich JL
    11. Spudich EN
    12. DeLong EF

    (2000) Bacterial rhodopsin: evidence for a new type of phototrophy in the sea

    Science (New York, N.Y.) 289:1902–1906.

    https://doi.org/10.1126/science.289.5486.1902

    • PubMed
    • Google Scholar
12. 1. Blanc-Mathieu R
    2. Dahle H
    3. Hofgaard A
    4. Brandt D
    5. Ban H
    6. Kalinowski J
    7. Ogata H
    8. Sandaa RA

    (2021) A persistent giant algal virus, with A unique morphology, encodes an unprecedented number of genes involved in energy metabolism

    Journal of Virology 20:JVI.02446-20.

    https://doi.org/10.1128/JVI.02446-20

    • PubMed
    • Google Scholar
13. 1. Blankenship RE

    (2010) Early evolution of photosynthesis

    Plant Physiology 154:434–438.

    https://doi.org/10.1104/pp.110.161687

    • PubMed
    • Google Scholar
14. 1. Brum JR
    2. Sullivan MB

    (2015) Rising to the challenge: accelerated pace of discovery transforms marine virology

    Nature Reviews. Microbiology 13:147–159.

    https://doi.org/10.1038/nrmicro3404

    • PubMed
    • Google Scholar
15. 1. Bryant DA
    2. Frigaard NU

    (2006) Prokaryotic photosynthesis and phototrophy illuminated

    Trends in Microbiology 14:488–496.

    https://doi.org/10.1016/j.tim.2006.09.001

    • PubMed
    • Google Scholar
16. 1. Buhr ED
    2. Yue WWS
    3. Ren X
    4. Jiang Z
    5. Liao HWR
    6. Mei X
    7. Vemaraju S
    8. Nguyen MT
    9. Reed RR
    10. Lang RA
    11. Yau KW
    12. Van Gelder RN

    (2015) Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea

    PNAS 112:13093–13098.

    https://doi.org/10.1073/pnas.1516259112

    • PubMed
    • Google Scholar
17. Software

    1. Butterworth PJ

    (2005)

    Lehninger: Principles of Biochemistry Cell Biochemistry and Function

    Lehninger.
18. 1. Campos-Sandoval JA
    2. López de la Oliva AR
    3. Lobo C
    4. Segura JA
    5. Matés JM
    6. Alonso FJ
    7. Márquez J

    (2007) Expression of functional human glutaminase in baculovirus system: affinity purification, kinetic and molecular characterization

    The International Journal of Biochemistry & Cell Biology 39:765–773.

    https://doi.org/10.1016/j.biocel.2006.12.002

    • PubMed
    • Google Scholar
19. 1. Chelkha N
    2. Levasseur A
    3. La Scola B
    4. Colson P

    (2020) Host-virus interactions and defense mechanisms for giant viruses

    Annals of the New York Academy of Sciences 1486:39–57.

    https://doi.org/10.1111/nyas.14469

    • PubMed
    • Google Scholar
20. 1. Claverie JM
    2. Abergel C

    (2010) Mimivirus: the emerging paradox of quasi-autonomous viruses

    Trends in Genetics 26:431–437.

    https://doi.org/10.1016/j.tig.2010.07.003

    • PubMed
    • Google Scholar
21. 1. Colson P
    2. De Lamballerie X
    3. Yutin N
    4. Asgari S
    5. Bigot Y
    6. Bideshi DK
    7. Cheng X-W
    8. Federici BA
    9. Van Etten JL
    10. Koonin EV
    11. La Scola B
    12. Raoult D

    (2013) “Megavirales”, a proposed new order for eukaryotic nucleocytoplasmic large DNA viruses

    Archives of Virology 158:2517–2521.

    https://doi.org/10.1007/s00705-013-1768-6

    • PubMed
    • Google Scholar
22. 1. Coutinho FH
    2. Silveira CB
    3. Gregoracci GB
    4. Thompson CC
    5. Edwards RA
    6. Brussaard CPD
    7. Dutilh BE
    8. Thompson FL

    (2017) Marine viruses discovered via metagenomics shed light on viral strategies throughout the oceans

    Nature Communications 8:15955.

    https://doi.org/10.1038/ncomms15955

    • PubMed
    • Google Scholar
23. 1. De Souza FG
    2. Abrahão JS
    3. Rodrigues RAL

    (2021) Comparative Analysis of Transcriptional Regulation Patterns: Understanding the Gene Expression Profile in Nucleocytoviricota

    Pathogens (Basel, Switzerland) 10:935.

    https://doi.org/10.3390/pathogens10080935

    • Google Scholar
24. 1. Driscoll TP
    2. Verhoeve VI
    3. Guillotte ML
    4. Lehman SS
    5. Rennoll SA
    6. Beier-Sexton M
    7. Rahman MS
    8. Azad AF
    9. Gillespie JJ

    (2017) Wholly Rickettsia! Reconstructed Metabolic Profile of the Quintessential Bacterial Parasite of Eukaryotic Cells

    MBio 8:e00859-17.

    https://doi.org/10.1128/mBio.00859-17

    • PubMed
    • Google Scholar
25. 1. Dupré J
    2. O’Malley MA

    (2009) Varieties of Living Things: Life at the Intersection of Lineage and Metabolism

    Philosophy and Theory in Biology 1:e003.

    https://doi.org/10.3998/ptb.6959004.0001.003

    • Google Scholar
26. 1. Endo H
    2. Blanc-Mathieu R
    3. Li Y
    4. Salazar G
    5. Henry N
    6. Labadie K
    7. de Vargas C
    8. Sullivan MB
    9. Bowler C
    10. Wincker P
    11. Karp-Boss L
    12. Sunagawa S
    13. Ogata H

    (2020) Biogeography of marine giant viruses reveals their interplay with eukaryotes and ecological functions

    Nature Ecology & Evolution 4:1639–1649.

    https://doi.org/10.1038/s41559-020-01288-w

    • PubMed
    • Google Scholar
27. 1. Fischer MG
    2. Allen MJ
    3. Wilson WH
    4. Suttle CA

    (2010) Giant virus with a remarkable complement of genes infects marine zooplankton

    PNAS 107:19508–19513.

    https://doi.org/10.1073/pnas.1007615107

    • PubMed
    • Google Scholar
28. 1. Forterre P

    (2013) The virocell concept and environmental microbiology

    The ISME Journal 7:233–236.

    https://doi.org/10.1038/ismej.2012.110

    • PubMed
    • Google Scholar
29. 1. Fridman S
    2. Flores-Uribe J
    3. Larom S
    4. Alalouf O
    5. Liran O
    6. Yacoby I
    7. Salama F
    8. Bailleul B
    9. Rappaport F
    10. Ziv T
    11. Sharon I
    12. Cornejo-Castillo FM
    13. Philosof A
    14. Dupont CL
    15. Sánchez P
    16. Acinas SG
    17. Rohwer FL
    18. Lindell D
    19. Béjà O

    (2017) A myovirus encoding both photosystem I and II proteins enhances cyclic electron flow in infected Prochlorococcus cells

    Nature Microbiology 2:1350–1357.

    https://doi.org/10.1038/s41564-017-0002-9

    • PubMed
    • Google Scholar
30. 1. Friedrich B
    2. Schwartz E

    (1993) Molecular biology of hydrogen utilization in aerobic chemolithotrophs

    Annual Review of Microbiology 47:351–383.

    https://doi.org/10.1146/annurev.mi.47.100193.002031

    • PubMed
    • Google Scholar
31. Book

    1. Friedrich CG

    (1997) Physiology and Genetics of Sulfur-oxidizing Bacteria

    In: Poole RK, editors. Advances in Microbial Physiology. Academic Press. pp. 235–289.

    https://doi.org/10.1016/S0065-2911(08)60018-1

    • Google Scholar
32. 1. Frigaard NU
    2. Martinez A
    3. Mincer TJ
    4. DeLong EF

    (2006) Proteorhodopsin lateral gene transfer between marine planktonic Bacteria and Archaea

    Nature 439:847–850.

    https://doi.org/10.1038/nature04435

    • PubMed
    • Google Scholar
33. 1. Frohns F
    2. Käsmann A
    3. Kramer D
    4. Schäfer B
    5. Mehmel M
    6. Kang M
    7. Van Etten JL
    8. Gazzarrini S
    9. Moroni A
    10. Thiel G

    (2006) Potassium ion channels of Chlorella viruses cause rapid depolarization of host cells during infection

    Journal of Virology 80:2437–2444.

    https://doi.org/10.1128/JVI.80.5.2437-2444.2006

    • PubMed
    • Google Scholar
34. 1. Gann ER
    2. Xian Y
    3. Abraham PE
    4. Hettich RL
    5. Reynolds TB
    6. Xiao C
    7. Wilhelm SW

    (2020) Structural and Proteomic Studies of the Aureococcus anophagefferens Virus Demonstrate a Global Distribution of Virus-Encoded Carbohydrate Processing

    Frontiers in Microbiology 11:2047.

    https://doi.org/10.3389/fmicb.2020.02047

    • PubMed
    • Google Scholar
35. Thesis

    1. Gehre L

    (2015) Chlamydia trachomatis hijacks energy stores from the host and accumulates glycogen in the inclusion lumen through a dual pathway

    Université Pierre et Marie Curie.

    https://tel.archives-ouvertes.fr/tel-01333744/document

    • Google Scholar
36. 1. Glevarec G
    2. Bouton S
    3. Jaspard E
    4. Riou MT
    5. Cliquet JB
    6. Suzuki A
    7. Limami AM

    (2004) Respective roles of the glutamine synthetase/glutamate synthase cycle and glutamate dehydrogenase in ammonium and amino acid metabolism during germination and post-germinative growth in the model legume Medicago truncatula

    Planta 219:286–297.

    https://doi.org/10.1007/s00425-004-1214-9

    • PubMed
    • Google Scholar
37. 1. Ha AD
    2. Moniruzzaman M
    3. Aylward FO

    (2021) High Transcriptional Activity and Diverse Functional Repertoires of Hundreds of Giant Viruses in a Coastal Marine System

    MSystems 6:e0029321.

    https://doi.org/10.1128/mSystems.00293-21

    • PubMed
    • Google Scholar
38. 1. Herbik A
    2. Bölling C
    3. Buckhout TJ

    (2002) The involvement of a multicopper oxidase in iron uptake by the green algae Chlamydomonas reinhardtii

    Plant Physiology 130:2039–2048.

    https://doi.org/10.1104/pp.013060

    • PubMed
    • Google Scholar
39. 1. Hogle SL
    2. Dupont CL
    3. Hopkinson BM
    4. King AL
    5. Buck KN
    6. Roe KL
    7. Stuart RK
    8. Allen AE
    9. Mann EL
    10. Johnson ZI
    11. Barbeau KA

    (2018) Pervasive iron limitation at subsurface chlorophyll maxima of the California Current

    PNAS 115:13300–13305.

    https://doi.org/10.1073/pnas.1813192115

    • PubMed
    • Google Scholar
40. 1. Hosokawa N
    2. Takahashi H
    3. Aoki K
    4. Takemura M

    (2021) Draft Genome Sequence of Pandoravirus japonicus Isolated from the Sabaishi River, Niigata, Japan

    Microbiology Resource Announcements 10:19.

    https://doi.org/10.1128/MRA.00365-21

    • PubMed
    • Google Scholar
41. 1. Hothersall JS
    2. Ahmed A

    (2013) Metabolic fate of the increased yeast amino Acid uptake subsequent to catabolite derepression

    Journal of Amino Acids 2013:461901.

    https://doi.org/10.1155/2013/461901

    • PubMed
    • Google Scholar
42. 1. Howard-Varona C
    2. Lindback MM
    3. Bastien GE
    4. Solonenko N
    5. Zayed AA
    6. Jang H
    7. Andreopoulos B
    8. Brewer HM
    9. Glavina Del Rio T
    10. Adkins JN
    11. Paul S
    12. Sullivan MB
    13. Duhaime MB

    (2020) Phage-specific metabolic reprogramming of virocells

    The ISME Journal 14:881–895.

    https://doi.org/10.1038/s41396-019-0580-z

    • PubMed
    • Google Scholar
43. 1. Hu W
    2. Zhang C
    3. Wu R
    4. Sun Y
    5. Levine A
    6. Feng Z

    (2010) Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function

    PNAS 107:7455–7460.

    https://doi.org/10.1073/pnas.1001006107

    • PubMed
    • Google Scholar
44. 1. Hurwitz BL
    2. Hallam SJ
    3. Sullivan MB

    (2013) Metabolic reprogramming by viruses in the sunlit and dark ocean

    Genome Biology 14:R123.

    https://doi.org/10.1186/gb-2013-14-11-r123

    • PubMed
    • Google Scholar
45. 1. Hurwitz BL
    2. U’Ren JM

    (2016) Viral metabolic reprogramming in marine ecosystems

    Current Opinion in Microbiology 31:161–168.

    https://doi.org/10.1016/j.mib.2016.04.002

    • PubMed
    • Google Scholar
46. 1. Jetten MS
    2. Strous M
    3. van de Pas-Schoonen KT
    4. Schalk J
    5. van Dongen UG
    6. van de Graaf AA
    7. Logemann S
    8. Muyzer G
    9. van Loosdrecht MC
    10. Kuenen JG

    (1998) The anaerobic oxidation of ammonium

    FEMS Microbiology Reviews 22:421–437.

    https://doi.org/10.1111/j.1574-6976.1998.tb00379.x

    • PubMed
    • Google Scholar
47. 1. Juneau P
    2. Lawrence JE
    3. Suttle CA
    4. Harrison PJ

    (2003) Effects of viral infection on photosynthetic processes in the bloom-forming alga Heterosigma akashiwo

    Aquatic Microbial Ecology 31:9–17.

    https://doi.org/10.3354/ame031009

    • Google Scholar
48. 1. Knappe J
    2. Blaschkowski HP
    3. Gröbner P
    4. Schmitt T

    (1974) Pyruvate formate-lyase of Escherichia coli: the acetyl-enzyme intermediate

    European Journal of Biochemistry 50:253–263.

    https://doi.org/10.1111/j.1432-1033.1974.tb03894.x

    • PubMed
    • Google Scholar
49. 1. Krebs HA
    2. Johnson WA

    (1937) Acetopyruvic acid (alphagamma-diketovaleric acid) as an intermediate metabolite in animal tissues

    The Biochemical Journal 31:772–779.

    https://doi.org/10.1042/bj0310772

    • PubMed
    • Google Scholar
50. 1. Ku C
    2. Sheyn U
    3. Sebé-Pedrós A
    4. Ben-Dor S
    5. Schatz D
    6. Tanay A
    7. Rosenwasser S
    8. Vardi A

    (2020) A single-cell view on alga-virus interactions reveals sequential transcriptional programs and infection states

    Science Advances 6:eaba4137.

    https://doi.org/10.1126/sciadv.aba4137

    • PubMed
    • Google Scholar
51. Book

    1. Kumari A

    (2018) Chapter 1 - Glycolysis

    In: Kumari A, editors. Sweet Biochemistry. Academic Press. pp. 1–5.

    https://doi.org/10.1016/B978-0-12-814453-4.00001-7

    • Google Scholar
52. 1. La Scola B
    2. Audic S
    3. Robert C
    4. Jungang L
    5. de Lamballerie X
    6. Drancourt M
    7. Birtles R
    8. Claverie JM
    9. Raoult D

    (2003) A giant virus in amoebae

    Science (New York, N.Y.) 299:2033.

    https://doi.org/10.1126/science.1081867

    • PubMed
    • Google Scholar
53. 1. Lairson LL
    2. Henrissat B
    3. Davies GJ
    4. Withers SG

    (2008) Glycosyltransferases: structures, functions, and mechanisms

    Annual Review of Biochemistry 77:521–555.

    https://doi.org/10.1146/annurev.biochem.76.061005.092322

    • PubMed
    • Google Scholar
54. 1. Lamb DC
    2. Follmer AH
    3. Goldstone JV
    4. Nelson DR
    5. Warrilow AG
    6. Price CL
    7. True MY
    8. Kelly SL
    9. Poulos TL
    10. Stegeman JJ

    (2019) On the occurrence of cytochrome P450 in viruses

    PNAS 116:12343–12352.

    https://doi.org/10.1073/pnas.1901080116

    • PubMed
    • Google Scholar
55. 1. Lartigue A
    2. Burlat B
    3. Coutard B
    4. Chaspoul F
    5. Claverie JM
    6. Abergel C

    (2015) The megavirus chilensis Cu,Zn-superoxide dismutase: the first viral structure of a typical cellular copper chaperone-independent hyperstable dimeric enzyme

    Journal of Virology 89:824–832.

    https://doi.org/10.1128/JVI.02588-14

    • PubMed
    • Google Scholar
56. 1. Legendre M
    2. Bartoli J
    3. Shmakova L
    4. Jeudy S
    5. Labadie K
    6. Adrait A
    7. Lescot M
    8. Poirot O
    9. Bertaux L
    10. Bruley C
    11. Couté Y
    12. Rivkina E
    13. Abergel C
    14. Claverie JM

    (2014) Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology

    PNAS 111:4274–4279.

    https://doi.org/10.1073/pnas.1320670111

    • PubMed
    • Google Scholar
57. 1. Legendre M
    2. Lartigue A
    3. Bertaux L
    4. Jeudy S
    5. Bartoli J
    6. Lescot M
    7. Alempic JM
    8. Ramus C
    9. Bruley C
    10. Labadie K
    11. Shmakova L
    12. Rivkina E
    13. Couté Y
    14. Abergel C
    15. Claverie JM

    (2015) In-depth study of Mollivirus sibericum, a new 30,000-y-old giant virus infecting Acanthamoeba

    PNAS 112:E5327–E5335.

    https://doi.org/10.1073/pnas.1510795112

    • PubMed
    • Google Scholar
58. 1. Legendre M
    2. Fabre E
    3. Poirot O
    4. Jeudy S
    5. Lartigue A
    6. Alempic J-M
    7. Beucher L
    8. Philippe N
    9. Bertaux L
    10. Christo-Foroux E
    11. Labadie K
    12. Couté Y
    13. Abergel C
    14. Claverie J-M

    (2018) Diversity and evolution of the emerging Pandoraviridae family

    Nature Communications 9:1–12.

    https://doi.org/10.1038/s41467-018-04698-4

    • PubMed
    • Google Scholar
59. Book

    1. Lehninger AL
    2. Nelson DL
    3. Cox MM

    (2004)

    Lehninger Principles of Biochemistry

    Wort Publishers.

    • Google Scholar
60. 1. Lin S
    2. Zhang H
    3. Zhuang Y
    4. Tran B
    5. Gill J

    (2010) Spliced leader-based metatranscriptomic analyses lead to recognition of hidden genomic features in dinoflagellates

    PNAS 107:20033–20038.

    https://doi.org/10.1073/pnas.1007246107

    • PubMed
    • Google Scholar
61. 1. Lindell D
    2. Jaffe JD
    3. Johnson ZI
    4. Church GM
    5. Chisholm SW

    (2005) Photosynthesis genes in marine viruses yield proteins during host infection

    Nature 438:86–89.

    https://doi.org/10.1038/nature04111

    • PubMed
    • Google Scholar
62. 1. Lovley DR
    2. Fraga JL
    3. Blunt-Harris EL
    4. Hayes LA
    5. Phillips EJP
    6. Coates JD

    (1998) Humic Substances as a Mediator for Microbially Catalyzed Metal Reduction

    Acta Hydrochimica et Hydrobiologica 26:152–157.

    https://doi.org/10.1002/(SICI)1521-401X(199805)26:3<152::AID-AHEH152>3.0.CO;2-D

    • Google Scholar
63. 1. Lovley DR
    2. Coates JD

    (2000) Novel forms of anaerobic respiration of environmental relevance

    Current Opinion in Microbiology 3:252–256.

    https://doi.org/10.1016/s1369-5274(00)00085-0

    • PubMed
    • Google Scholar
64. Software

    1. Lovley D

    (2002) Dissimilatory Metal Reduction: From Early Life to Bioremediation

    Bepress.

    https://works.bepress.com/derek_lovley/189/
65. Book

    1. Luria SE

    (1959)

    Virus Growth and Variation

    Cambridge University Press.

    • Google Scholar
66. 1. Márquez LM
    2. Redman RS
    3. Rodriguez RJ
    4. Roossinck MJ

    (2007) A virus in A fungus in A plant: three-way symbiosis required for thermal tolerance

    Science (New York, N.Y.) 315:513–515.

    https://doi.org/10.1126/science.1136237

    • PubMed
    • Google Scholar
67. 1. Maughan R

    (2009) Carbohydrate metabolism

    Surgery (Oxford) 27:6–10.

    https://doi.org/10.1016/j.mpsur.2008.12.002

    • Google Scholar
68. 1. Meléndez-Hevia E
    2. Waddell TG
    3. Cascante M

    (1996) The puzzle of the Krebs citric acid cycle: assembling the pieces of chemically feasible reactions, and opportunism in the design of metabolic pathways during evolution

    Journal of Molecular Evolution 43:293–303.

    https://doi.org/10.1007/BF02338838

    • PubMed
    • Google Scholar
69. 1. Miller SM
    2. Magasanik B

    (1990) Role of NAD-linked glutamate dehydrogenase in nitrogen metabolism in Saccharomyces cerevisiae

    Journal of Bacteriology 172:4927–4935.

    https://doi.org/10.1128/jb.172.9.4927-4935.1990

    • PubMed
    • Google Scholar
70. 1. Mohammed Ali AM
    2. Kawasaki T
    3. Yamada T

    (2005) Genetic rearrangements on the Chlorovirus genome that switch between hyaluronan synthesis and chitin synthesis

    Virology 342:102–110.

    https://doi.org/10.1016/j.virol.2005.07.026

    • PubMed
    • Google Scholar
71. 1. Monier A
    2. Pagarete A
    3. de Vargas C
    4. Allen MJ
    5. Read B
    6. Claverie J-M
    7. Ogata H

    (2009) Horizontal gene transfer of an entire metabolic pathway between a eukaryotic alga and its DNA virus

    Genome Research 19:1441–1449.

    https://doi.org/10.1101/gr.091686.109

    • PubMed
    • Google Scholar
72. 1. Monier A
    2. Chambouvet A
    3. Milner DS
    4. Attah V
    5. Terrado R
    6. Lovejoy C
    7. Moreau H
    8. Santoro AE
    9. Derelle É
    10. Richards TA

    (2017) Host-derived viral transporter protein for nitrogen uptake in infected marine phytoplankton

    PNAS 114:E7489–E7498.

    https://doi.org/10.1073/pnas.1708097114

    • PubMed
    • Google Scholar
73. 1. Moniruzzaman M
    2. LeCleir GR
    3. Brown CM
    4. Gobler CJ
    5. Bidle KD
    6. Wilson WH
    7. Wilhelm SW

    (2014) Genome of brown tide virus (AaV), the little giant of the Megaviridae, elucidates NCLDV genome expansion and host-virus coevolution

    Virology 466–467:60–70.

    https://doi.org/10.1016/j.virol.2014.06.031

    • PubMed
    • Google Scholar
74. 1. Moniruzzaman M
    2. Wurch LL
    3. Alexander H
    4. Dyhrman ST
    5. Gobler CJ
    6. Wilhelm SW

    (2017) Virus-host relationships of marine single-celled eukaryotes resolved from metatranscriptomics

    Nature Communications 8:16054.

    https://doi.org/10.1038/ncomms16054

    • PubMed
    • Google Scholar
75. 1. Moniruzzaman M
    2. Gann ER
    3. Wilhelm SW

    (2018) Infection by A Giant Virus (AaV) Induces Widespread Physiological Reprogramming in Aureococcus anophagefferens CCMP1984 - A Harmful Bloom Algae

    Frontiers in Microbiology 9:752.

    https://doi.org/10.3389/fmicb.2018.00752

    • PubMed
    • Google Scholar
76. 1. Moniruzzaman M
    2. Martinez-Gutierrez CA
    3. Weinheimer AR
    4. Aylward FO

    (2020) Dynamic genome evolution and complex virocell metabolism of globally-distributed giant viruses

    Nature Communications 11:1710.

    https://doi.org/10.1038/s41467-020-15507-2

    • PubMed
    • Google Scholar
77. 1. Moreira D
    2. Brochier-Armanet C

    (2008) Giant viruses, giant chimeras: the multiple evolutionary histories of Mimivirus genes

    BMC Evolutionary Biology 8:12.

    https://doi.org/10.1186/1471-2148-8-12

    • PubMed
    • Google Scholar
78. 1. Moreira D
    2. López-García P

    (2009) Ten reasons to exclude viruses from the tree of life

    Nature Reviews. Microbiology 7:306–311.

    https://doi.org/10.1038/nrmicro2108

    • PubMed
    • Google Scholar
79. 1. Müller M
    2. Mentel M
    3. van Hellemond JJ
    4. Henze K
    5. Woehle C
    6. Gould SB
    7. Yu R-Y
    8. van der Giezen M
    9. Tielens AGM
    10. Martin WF

    (2012) Biochemistry and evolution of anaerobic energy metabolism in eukaryotes

    Microbiology and Molecular Biology Reviews 76:444–495.

    https://doi.org/10.1128/MMBR.05024-11

    • PubMed
    • Google Scholar
80. 1. Needham DM
    2. Yoshizawa S
    3. Hosaka T
    4. Poirier C
    5. Choi CJ
    6. Hehenberger E
    7. Irwin NAT
    8. Wilken S
    9. Yung CM
    10. Bachy C
    11. Kurihara R
    12. Nakajima Y
    13. Kojima K
    14. Kimura-Someya T
    15. Leonard G
    16. Malmstrom RR
    17. Mende DR
    18. Olson DK
    19. Sudo Y
    20. Sudek S
    21. Richards TA
    22. DeLong EF
    23. Keeling PJ
    24. Santoro AE
    25. Shirouzu M
    26. Iwasaki W
    27. Worden AZ

    (2019) A distinct lineage of giant viruses brings A rhodopsin photosystem to unicellular marine predators

    PNAS 116:20574–20583.

    https://doi.org/10.1073/pnas.1907517116

    • PubMed
    • Google Scholar
81. Book

    1. Nelson DL
    2. Cox MM

    (2017)

    Lehninger Principles of Biochemistry

    W.H. Freeman.

    • Google Scholar
82. 1. Neupärtl M
    2. Meyer C
    3. Woll I
    4. Frohns F
    5. Kang M
    6. Van Etten JL
    7. Kramer D
    8. Hertel B
    9. Moroni A
    10. Thiel G

    (2008) Chlorella viruses evoke a rapid release of K+ from host cells during the early phase of infection

    Virology 372:340–348.

    https://doi.org/10.1016/j.virol.2007.10.024

    • PubMed
    • Google Scholar
83. 1. Nissimov JI
    2. Talmy D
    3. Haramaty L
    4. Fredricks HF
    5. Zelzion E
    6. Knowles B
    7. Eren AM
    8. Vandzura R
    9. Laber CP
    10. Schieler BM
    11. Johns CT
    12. More KD
    13. Coolen MJL
    14. Follows MJ
    15. Bhattacharya D
    16. Van Mooy BAS
    17. Bidle KD

    (2019) Biochemical diversity of glycosphingolipid biosynthesis as a driver of Coccolithovirus competitive ecology

    Environmental Microbiology 21:2182–2197.

    https://doi.org/10.1111/1462-2920.14633

    • PubMed
    • Google Scholar
84. 1. Noor E
    2. Eden E
    3. Milo R
    4. Alon U

    (2010) Central carbon metabolism as a minimal biochemical walk between precursors for biomass and energy

    Molecular Cell 39:809–820.

    https://doi.org/10.1016/j.molcel.2010.08.031

    • PubMed
    • Google Scholar
85. 1. Olson JM

    (2006) Photosynthesis in the Archean era

    Photosynthesis Research 88:109–117.

    https://doi.org/10.1007/s11120-006-9040-5

    • Google Scholar
86. 1. Oyedotun KS
    2. Lemire BD

    (2004) The quaternary structure of the Saccharomyces cerevisiae succinate dehydrogenase Homology modeling, cofactor docking, and molecular dynamics simulation studies

    The Journal of Biological Chemistry 279:9424–9431.

    https://doi.org/10.1074/jbc.M311876200

    • PubMed
    • Google Scholar
87. 1. Philippe N
    2. Legendre M
    3. Doutre G
    4. Couté Y
    5. Poirot O
    6. Lescot M
    7. Arslan D
    8. Seltzer V
    9. Bertaux L
    10. Bruley C
    11. Garin J
    12. Claverie J-M
    13. Abergel C

    (2013) Pandoraviruses: amoeba viruses with genomes up to 2.5 Mb reaching that of parasitic eukaryotes

    Science (New York, N.Y.) 341:281–286.

    https://doi.org/10.1126/science.1239181

    • PubMed
    • Google Scholar
88. 1. Piacente F
    2. Marin M
    3. Molinaro A
    4. De Castro C
    5. Seltzer V
    6. Salis A
    7. Damonte G
    8. Bernardi C
    9. Claverie J-M
    10. Abergel C
    11. Tonetti M

    (2012) Giant DNA virus mimivirus encodes pathway for biosynthesis of unusual sugar 4-amino-4,6-dideoxy-D-glucose (Viosamine

    The Journal of Biological Chemistry 287:3009–3018.

    https://doi.org/10.1074/jbc.M111.314559

    • PubMed
    • Google Scholar
89. 1. Piacente F
    2. Bernardi C
    3. Marin M
    4. Blanc G
    5. Abergel C
    6. Tonetti MG

    (2014) Characterization of a UDP-N-acetylglucosamine biosynthetic pathway encoded by the giant DNA virus Mimivirus

    Glycobiology 24:51–61.

    https://doi.org/10.1093/glycob/cwt089

    • PubMed
    • Google Scholar
90. 1. Piacente F
    2. Gaglianone M
    3. Laugieri ME
    4. Tonetti MG

    (2015) The Autonomous Glycosylation of Large DNA Viruses

    International Journal of Molecular Sciences 16:29315–29328.

    https://doi.org/10.3390/ijms161226169

    • PubMed
    • Google Scholar
91. 1. Plaitakis A
    2. Kalef-Ezra E
    3. Kotzamani D
    4. Zaganas I
    5. Spanaki C

    (2017) The Glutamate Dehydrogenase Pathway and Its Roles in Cell and Tissue Biology in Health and Disease

    Biology 6:E11.

    https://doi.org/10.3390/biology6010011

    • PubMed
    • Google Scholar
92. 1. Potter S
    2. Fothergill-Gilmore LA

    (1993) Molecular evolution: The origin of glycolysis

    Biochemical Education 21:45–48.

    https://doi.org/10.1016/0307-4412(93)90018-U

    • Google Scholar
93. 1. Pratama AA
    2. Bolduc B
    3. Zayed AA
    4. Zhong Z-P
    5. Guo J
    6. Vik DR
    7. Gazitúa MC
    8. Wainaina JM
    9. Roux S
    10. Sullivan MB

    (2021) Expanding standards in viromics: in silico evaluation of dsDNA viral genome identification, classification, and auxiliary metabolic gene curation

    PeerJ 9:e11447.

    https://doi.org/10.7717/peerj.11447

    • PubMed
    • Google Scholar
94. 1. Raoult D
    2. Audic S
    3. Robert C
    4. Abergel C
    5. Renesto P
    6. Ogata H
    7. La Scola B
    8. Suzan M
    9. Claverie J-M

    (2004) The 1.2-megabase genome sequence of Mimivirus

    Science (New York, N.Y.) 306:1344–1350.

    https://doi.org/10.1126/science.1101485

    • PubMed
    • Google Scholar
95. 1. Raoult D
    2. Forterre P

    (2008a) Redefining viruses: lessons from Mimivirus

    Nature Reviews. Microbiology 6:315–319.

    https://doi.org/10.1038/nrmicro1858

    • PubMed
    • Google Scholar
96. 1. Raoult D
    2. Forterre P

    (2008b) What makes a virus a virus: reply from Raoult and Forterre

    Nature Reviews Microbiology 6:643.

    https://doi.org/10.1038/nrmicro1858-c2

    • Google Scholar
97. Book

    1. Regenmortel MHVV

    (2010) The Nature and Classification of Viruses, Topley & Wilson’s Microbiology and Microbial Infections

    American Cancer Society.

    https://doi.org/10.1002/9780470688618.taw0209

    • Google Scholar
98. 1. Rodrigues RAL
    2. Arantes TS
    3. Oliveira GP
    4. Dos Santos Silva LK
    5. Abrahão JS

    (2019) The Complex Nature of Tupanviruses

    Advances in Virus Research 103:135–166.

    https://doi.org/10.1016/bs.aivir.2018.09.001

    • PubMed
    • Google Scholar
99. Book

    1. Rodwell VW
    2. Bender DA
    3. Botham KM
    4. Kennelly PJ
    5. Weil PA

    (2015)

    Harper’s Illustrated Biochemistry

    McGraw Hill Medical.

    • Google Scholar
100. 1. Rolland C
     2. Andreani J
     3. Louazani AC
     4. Aherfi S
     5. Francis R
     6. Rodrigues R
     7. Silva LS
     8. Sahmi D
     9. Mougari S
     10. Chelkha N
     11. Bekliz M
     12. Silva L
     13. Assis F
     14. Dornas F
     15. Khalil JYB
     16. Pagnier I
     17. Desnues C
     18. Levasseur A
     19. Colson P
     20. Abrahão J
     21. La Scola B

     (2019) Discovery and Further Studies on Giant Viruses at the IHU Mediterranee Infection That Modified the Perception of the Virosphere

     Viruses 11:E312.

     https://doi.org/10.3390/v11040312

     • PubMed
     • Google Scholar
101. 1. Rosenwasser S
     2. Ziv C
     3. Creveld SG
     4. Vardi A

     (2016) Virocell Metabolism: Metabolic Innovations During Host-Virus Interactions in the Ocean

     Trends in Microbiology 24:821–832.

     https://doi.org/10.1016/j.tim.2016.06.006

     • PubMed
     • Google Scholar
102. 1. Saikia S
     2. Oliveira D
     3. Hu G
     4. Kronstad J

     (2014) Role of ferric reductases in iron acquisition and virulence in the fungal pathogen Cryptococcus neoformans

     Infection and Immunity 82:839–850.

     https://doi.org/10.1128/IAI.01357-13

     • PubMed
     • Google Scholar
103. Book

     1. Sanders LM

     (2016) Carbohydrate: Digestion, Absorption and Metabolism

     In: Caballero B, Finglas PM, Toldrá F, editors. Encyclopedia of Food and Health. Oxford: Academic Press. pp. 643–650.

     https://doi.org/10.1016/B978-0-12-384947-2.00114-8

     • Google Scholar
104. 1. Santini S
     2. Jeudy S
     3. Bartoli J
     4. Poirot O
     5. Lescot M
     6. Abergel C
     7. Claverie JM

     (2013) Genome of Phaeocystis globosa virus PgV-16T highlights the common ancestry of the largest known DNA viruses infecting eukaryotes

     PNAS 110:10800–10805.

     https://doi.org/10.1073/pnas.1303251110

     • Google Scholar
105. 1. Schröder I
     2. Johnson E
     3. de Vries S

     (2003) Microbial ferric iron reductases

     FEMS Microbiology Reviews 27:427–447.

     https://doi.org/10.1016/S0168-6445(03)00043-3

     • PubMed
     • Google Scholar
106. 1. Schulz F
     2. Yutin N
     3. Ivanova NN
     4. Ortega DR
     5. Lee TK
     6. Vierheilig J
     7. Daims H
     8. Horn M
     9. Wagner M
     10. Jensen GJ
     11. Kyrpides NC
     12. Koonin EV
     13. Woyke T

     (2017) Giant viruses with an expanded complement of translation system components

     Science (New York, N.Y.) 356:82–85.

     https://doi.org/10.1126/science.aal4657

     • PubMed
     • Google Scholar
107. 1. Schulz F
     2. Roux S
     3. Paez-Espino D
     4. Jungbluth S
     5. Walsh DA
     6. Denef VJ
     7. McMahon KD
     8. Konstantinidis KT
     9. Eloe-Fadrosh EA
     10. Kyrpides NC
     11. Woyke T

     (2020) Giant virus diversity and host interactions through global metagenomics

     Nature 578:432–436.

     https://doi.org/10.1038/s41586-020-1957-x

     • PubMed
     • Google Scholar
108. 1. Schvarcz CR
     2. Steward GF

     (2018) A giant virus infecting green algae encodes key fermentation genes

     Virology 518:423–433.

     https://doi.org/10.1016/j.virol.2018.03.010

     • PubMed
     • Google Scholar
109. 1. Sharon I
     2. Alperovitch A
     3. Rohwer F
     4. Haynes M
     5. Glaser F
     6. Atamna-Ismaeel N
     7. Pinter RY
     8. Partensky F
     9. Koonin EV
     10. Wolf YI
     11. Nelson N
     12. Béjà O

     (2009) Photosystem I gene cassettes are present in marine virus genomes

     Nature 461:258–262.

     https://doi.org/10.1038/nature08284

     • PubMed
     • Google Scholar
110. 1. Sheyn U
     2. Rosenwasser S
     3. Ben-Dor S
     4. Porat Z
     5. Vardi A

     (2016) Modulation of host ROS metabolism is essential for viral infection of a bloom-forming coccolithophore in the ocean

     The ISME Journal 10:1742–1754.

     https://doi.org/10.1038/ismej.2015.228

     • PubMed
     • Google Scholar
111. 1. Short SM

     (2012) The ecology of viruses that infect eukaryotic algae

     Environmental Microbiology 14:2253–2271.

     https://doi.org/10.1111/j.1462-2920.2012.02706.x

     • PubMed
     • Google Scholar
112. 1. Slamovits CH
     2. Okamoto N
     3. Burri L
     4. James ER
     5. Keeling PJ

     (2011) A bacterial proteorhodopsin proton pump in marine eukaryotes

     Nature Communications 2:183.

     https://doi.org/10.1038/ncomms1188

     • PubMed
     • Google Scholar
113. 1. Smith E
     2. Morowitz HJ

     (2004) Universality in intermediary metabolism

     PNAS 101:13168–13173.

     https://doi.org/10.1073/pnas.0404922101

     • PubMed
     • Google Scholar
114. 1. Sullivan MB
     2. Lindell D
     3. Lee JA
     4. Thompson LR
     5. Bielawski JP
     6. Chisholm SW

     (2006) Prevalence and evolution of core photosystem II genes in marine cyanobacterial viruses and their hosts

     PLOS Biology 4:e234.

     https://doi.org/10.1371/journal.pbio.0040234

     • PubMed
     • Google Scholar
115. 1. Sun L
     2. Adams B
     3. Gurnon JR
     4. Ye Y
     5. Van Etten JL

     (1999) Characterization of two chitinase genes and one chitosanase gene encoded by Chlorella virus PBCV-1

     Virology 263:376–387.

     https://doi.org/10.1006/viro.1999.9958

     • PubMed
     • Google Scholar
116. 1. Sun L
     2. Gurnon JR
     3. Adams BJ
     4. Graves MV
     5. Van Etten JL

     (2000) Characterization of a beta-1,3-glucanase encoded by chlorella virus PBCV-1

     Virology 276:27–36.

     https://doi.org/10.1006/viro.2000.0500

     • PubMed
     • Google Scholar
117. 1. Sun TW
     2. Yang CL
     3. Kao TT
     4. Wang TH
     5. Lai MW
     6. Ku C

     (2020) Host Range and Coding Potential of Eukaryotic Giant Viruses

     Viruses 12:E1337.

     https://doi.org/10.3390/v12111337

     • PubMed
     • Google Scholar
118. 1. Suttle CA

     (2005) Viruses in the sea

     Nature 437:356–361.

     https://doi.org/10.1038/nature04160

     • PubMed
     • Google Scholar
119. 1. Suttle CA

     (2007) Marine viruses--major players in the global ecosystem

     Nature Reviews. Microbiology 5:801–812.

     https://doi.org/10.1038/nrmicro1750

     • PubMed
     • Google Scholar
120. 1. Suttle CA

     (2016) Environmental microbiology: Viral diversity on the global stage

     Nature Microbiology 1:16205.

     https://doi.org/10.1038/nmicrobiol.2016.205

     • PubMed
     • Google Scholar
121. 1. Tonetti M
     2. Zanardi D
     3. Gurnon JR
     4. Fruscione F
     5. Armirotti A
     6. Damonte G
     7. Sturla L
     8. De Flora A
     9. Van Etten JL

     (2003) Paramecium bursaria Chlorella virus 1 encodes two enzymes involved in the biosynthesis of GDP-L-fucose and GDP-D-rhamnose

     The Journal of Biological Chemistry 278:21559–21565.

     https://doi.org/10.1074/jbc.M301543200

     • PubMed
     • Google Scholar
122. 1. Van Etten JL
     2. Agarkova I
     3. Dunigan DD
     4. Tonetti M
     5. De Castro C
     6. Duncan GA

     (2017) Chloroviruses Have a Sweet Tooth

     Viruses 9:E88.

     https://doi.org/10.3390/v9040088

     • PubMed
     • Google Scholar
123. 1. Vardi A
     2. Van Mooy BAS
     3. Fredricks HF
     4. Popendorf KJ
     5. Ossolinski JE
     6. Haramaty L
     7. Bidle KD

     (2009) Viral glycosphingolipids induce lytic infection and cell death in marine phytoplankton

     Science (New York, N.Y.) 326:861–865.

     https://doi.org/10.1126/science.1177322

     • PubMed
     • Google Scholar
124. Book

     1. Villarreal LP

     (2005) Viruses and the Evolution of Life

     John Wiley & Sons, Inc.

     https://doi.org/10.1128/9781555817626

     • Google Scholar
125. 1. Villarreal L
     2. Witzany G

     (2010) Viruses are essential agents within the roots and stem of the tree of life

     Journal of Theoretical Biology 262:698–710.

     https://doi.org/10.1016/j.jtbi.2009.10.014

     • PubMed
     • Google Scholar
126. 1. Wilson WH
     2. Schroeder DC
     3. Allen MJ
     4. Holden MTG
     5. Parkhill J
     6. Barrell BG
     7. Churcher C
     8. Hamlin N
     9. Mungall K
     10. Norbertczak H
     11. Quail MA
     12. Price C
     13. Rabbinowitsch E
     14. Walker D
     15. Craigon M
     16. Roy D
     17. Ghazal P

     (2005) Complete genome sequence and lytic phase transcription profile of a Coccolithovirus

     Science 309:1090–1092.

     https://doi.org/10.1126/science.1113109

     • PubMed
     • Google Scholar
127. 1. Yutin N
     2. Koonin EV

     (2012) Proteorhodopsin genes in giant viruses

     Biology Direct 7:34.

     https://doi.org/10.1186/1745-6150-7-34

     • PubMed
     • Google Scholar
128. 1. Yutin N
     2. Colson P
     3. Raoult D
     4. Koonin EV

     (2013) Mimiviridae: clusters of orthologous genes, reconstruction of gene repertoire evolution and proposed expansion of the giant virus family

     Virology Journal 10:106.

     https://doi.org/10.1186/1743-422X-10-106

     • PubMed
     • Google Scholar
129. 1. Zhou N
     2. Swamy KBS
     3. Leu JY
     4. McDonald MJ
     5. Galafassi S
     6. Compagno C
     7. Piškur J

     (2017) Coevolution with bacteria drives the evolution of aerobic fermentation in Lachancea kluyveri

     PLOS ONE 12:e0173318.

     https://doi.org/10.1371/journal.pone.0173318

     • PubMed
     • Google Scholar
130. 1. Zimmerman AE
     2. Howard-Varona C
     3. Needham DM
     4. John SG
     5. Worden AZ
     6. Sullivan MB
     7. Waldbauer JR
     8. Coleman ML

     (2020) Metabolic and biogeochemical consequences of viral infection in aquatic ecosystems

     Nature Reviews. Microbiology 18:21–34.

     https://doi.org/10.1038/s41579-019-0270-x

     • PubMed
     • Google Scholar

Author details

1. Djamal Brahim Belhaouari

   Microbes, Evolution, Phylogeny and Infection (MEPHI), UM63, Institut de Recherche pour le Développement (IRD), IHU Méditerranée Infection, Marseille, France, Aix-Marseille Université, Marseille, France

   Contribution

   Formal analysis, Writing – original draft

   Competing interests

   No competing interests declared

2. Gabriel Augusto Pires De Souza

   Microbes, Evolution, Phylogeny and Infection (MEPHI), UM63, Institut de Recherche pour le Développement (IRD), IHU Méditerranée Infection, Marseille, France, Aix-Marseille Université, Marseille, France

   Contribution

   Formal analysis, Writing – original draft

   Competing interests

   No competing interests declared

3. David C Lamb

   Faculty of Medicine, Health and Life Sciences, Institute of Life Science, Swansea University, Swansea, United Kingdom

   Contribution

   Formal analysis, Supervision, Writing – original draft, Writing – review and editing

   Competing interests

   No competing interests declared

4. Steven L Kelly

   Faculty of Medicine, Health and Life Sciences, Institute of Life Science, Swansea University, Swansea, United Kingdom

   Contribution

   Writing – original draft

   Competing interests

   No competing interests declared

5. Jared V Goldstone

   Biology Department, Woods Hole Oceanographic Institution, Woods Hole, United States

   Contribution

   Writing – review and editing

   Competing interests

   No competing interests declared

6. John J Stegeman

   Biology Department, Woods Hole Oceanographic Institution, Woods Hole, United States

   Contribution

   Writing – original draft, Writing – review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0001-8204-5357

7. Philippe Colson

   1. Microbes, Evolution, Phylogeny and Infection (MEPHI), UM63, Institut de Recherche pour le Développement (IRD), IHU Méditerranée Infection, Marseille, France, Aix-Marseille Université, Marseille, France
   2. Assistance Publique - Hôpitaux de Marseille (AP-HM), Marseille, France

   Contribution

   Validation

   Competing interests

   No competing interests declared

8. Bernard La Scola

   1. Microbes, Evolution, Phylogeny and Infection (MEPHI), UM63, Institut de Recherche pour le Développement (IRD), IHU Méditerranée Infection, Marseille, France, Aix-Marseille Université, Marseille, France
   2. Assistance Publique - Hôpitaux de Marseille (AP-HM), Marseille, France

   Contribution

   Validation, Writing – review and editing

   For correspondence

   bernard.la-scola@univ-amu.fr

   Competing interests

   No competing interests declared

9. Sarah Aherfi

   1. Microbes, Evolution, Phylogeny and Infection (MEPHI), UM63, Institut de Recherche pour le Développement (IRD), IHU Méditerranée Infection, Marseille, France, Aix-Marseille Université, Marseille, France
   2. Assistance Publique - Hôpitaux de Marseille (AP-HM), Marseille, France

   Contribution

   Formal analysis, Supervision, Validation, Writing – original draft, Writing – review and editing

   For correspondence

   sarah.aherfi@ap-hm.fr

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-5253-1757

• 2,096

  views

• 366

  downloads

• 12

  citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.