Family Of Giant Viruses Research Articles

Pithoviruses Are Invaded by Repeats That Contribute to Their Evolution and Divergence from Cedratviruses.

Pithoviridae are amoeba-infecting giant viruses possessing the largest viral particles known so far. Since the discovery of Pithovirus sibericum, recovered from a 30,000-yr-old permafrost sample, other pithoviruses, and related cedratviruses, were isolated from various terrestrial and aquatic samples. Here, we report the isolation and genome sequencing of 2 Pithoviridae from soil samples, in addition to 3 other recent isolates. Using the 12 available genome sequences, we conducted a thorough comparative genomic study of the Pithoviridae family to decipher the organization and evolution of their genomes. Our study reveals a nonuniform genome organization in 2 main regions: 1 concentrating core genes and another gene duplications. We also found that Pithoviridae genomes are more conservative than other families of giant viruses, with a low and stable proportion (5% to 7%) of genes originating from horizontal transfers. Genome size variation within the family is mainly due to variations in gene duplication rates (from 14% to 28%) and massive invasion by inverted repeats. While these repeated elements are absent from cedratviruses, repeat-rich regions cover as much as a quarter of the pithoviruses genomes. These regions, identified using a dedicated pipeline, are hotspots of mutations, gene capture events, and genomic rearrangements that contribute to their evolution.

Asfarviruses and Closely Related Giant Viruses.

Acanthamoeba polyphaga mimivirus, so called because of its "mimicking microbe", was discovered in 2003 and was the founding member of the first family of giant viruses isolated from amoeba. These giant viruses, present in various environments, have opened up a previously unexplored field of virology. Since 2003, many other giant viruses have been isolated, founding new families and taxonomical groups. These include a new giant virus which was isolated in 2015, the result of the first co-culture on Vermamoeba vermiformis. This new giant virus was named "Faustovirus". Its closest known relative at that time was African Swine Fever Virus. Pacmanvirus and Kaumoebavirus were subsequently discovered, exhibiting phylogenetic clustering with the two previous viruses and forming a new group with a putative common ancestor. In this study, we aimed to summarise the main features of the members of this group of giant viruses, including Abalone Asfarvirus, African Swine Fever Virus, Faustovirus, Pacmanvirus, and Kaumoebavirus.

A novel capsid protein network allows the characteristic internal membrane structure of Marseilleviridae giant viruses

Marseilleviridae is a family of giant viruses, showing a characteristic internal membrane with extrusions underneath the icosahedral vertices. However, such large objects, with a maximum diameter of 250 nm are technically difficult to examine at sub-nanometre resolution by cryo-electron microscopy. Here, we tested the utility of 1 MV high-voltage cryo-EM (cryo-HVEM) for single particle structural analysis (SPA) of giant viruses using tokyovirus, a species of Marseilleviridae, and revealed the capsid structure at 7.7 Å resolution. The capsid enclosing the viral DNA consisted primarily of four layers: (1) major capsid proteins (MCPs) and penton proteins, (2) minor capsid proteins (mCPs), (3) scaffold protein components (ScPCs), and (4) internal membrane. The mCPs showed a novel capsid lattice consisting of eight protein components. ScPCs connecting the icosahedral vertices supported the formation of the membrane extrusions, and possibly act like tape measure proteins reported in other giant viruses. The density on top of the MCP trimer was suggested to include glycoproteins. This is the first attempt at cryo-HVEM SPA. We found the primary limitations to be the lack of automated data acquisition and software support for collection and processing and thus achievable resolution. However, the results pave the way for using cryo-HVEM for structural analysis of larger biological specimens.

A small nucleosome from a weird virus with a fat genome

Valencia-Sánchez etal. (2021) and Liu etal. (2021) provide structural and biological insights about the existence and importance of a nucleosome-like particle in a family of giant viruses.

Comparative Analysis of Transcriptional Regulation Patterns: Understanding the Gene Expression Profile in Nucleocytoviricota.

The nucleocytoplasmic large DNA viruses (NCLDV) possess unique characteristics that have drawn the attention of the scientific community, and they are now classified in the phylum Nucleocytoviricota. They are characterized by sharing many genes and have their own transcriptional apparatus, which provides certain independence from their host’s machinery. Thus, the presence of a robust transcriptional apparatus has raised much discussion about the evolutionary aspects of these viruses and their genomes. Understanding the transcriptional process in NCLDV would provide information regarding their evolutionary history and a better comprehension of the biology of these viruses and their interaction with hosts. In this work, we reviewed NCLDV transcription and performed a comparative functional analysis of the groups of genes expressed at different times of infection of representatives of six different viral families of giant viruses. With this analysis, it was possible to observe a temporal profile of their gene expression and set of genes activated in specific phases throughout the multiplication cycle as a common characteristic of this group. Due to the lack of information regarding the transcriptional regulation process of this group of pathogens, we sought to provide information that contributes to and opens up the field for transcriptional studies of other viruses belonging to Nucleocytoviricota.

Marseilleviruses: An Update in 2021.

The family Marseilleviridae was the second family of giant viruses that was described in 2013, after the family Mimiviridae. Marseillevirus marseillevirus, isolated in 2007 by coculture on Acanthamoeba polyphaga, is the prototype member of this family. Afterward, the worldwide distribution of marseilleviruses was revealed through their isolation from samples of various types and sources. Thus, 62 were isolated from environmental water, one from soil, one from a dipteran, one from mussels, and two from asymptomatic humans, which led to the description of 67 marseillevirus isolates, including 21 by the IHU Méditerranée Infection in France. Recently, five marseillevirus genomes were assembled from deep sea sediment in Norway. Isolated marseilleviruses have ≈250 nm long icosahedral capsids and 348–404 kilobase long mosaic genomes that encode 386–545 predicted proteins. Comparative genomic analyses indicate that the family Marseilleviridae includes five lineages and possesses a pangenome composed of 3,082 clusters of genes. The detection of marseilleviruses in both symptomatic and asymptomatic humans in stool, blood, and lymph nodes, and an up-to-30-day persistence of marseillevirus in rats and mice, raise questions concerning their possible clinical significance that are still under investigation.

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

Viruses modulate the function(s) of environmentally relevant microbial populations, yet considerations of the metabolic capabilities of individual virus particles themselves are rare. We used shotgun proteomics to quantitatively identify 43 virus-encoded proteins packaged within purified Aureococcus anophagefferens Virus (AaV) particles, normalizing data to the per-virion level using a 9.5-Å-resolution molecular reconstruction of the 1900-Å (AaV) particle that we generated with cryogenic electron microscopy. This packaged proteome was used to determine similarities and differences between members of different giant virus families. We noted that proteins involved in sugar degradation and binding (e.g., carbohydrate lyases) were unique to AaV among characterized giant viruses. To determine the extent to which this virally encoded metabolic capability was ecologically relevant, we examined the TARA Oceans dataset and identified genes and transcripts of viral origin. Our analyses demonstrated that putative giant virus carbohydrate lyases represented up to 17% of the marine pool for this function. In total, our observations suggest that the AaV particle has potential prepackaged metabolic capabilities and that these may be found in other giant viruses that are widespread and abundant in global oceans.

Characterization of Mollivirus kamchatka, the First Modern Representative of the Proposed Molliviridae Family of Giant Viruses.

Microbes trapped in permanently frozen paleosoils (permafrost) are the focus of increasing research in the context of global warming. Our previous investigations led to the discovery and reactivation of two Acanthamoeba-infecting giant viruses, Mollivirus sibericum and Pithovirus sibericum, from a 30,000-year old permafrost layer. While several modern pithovirus strains have since been isolated, no contemporary mollivirus relative was found. We now describe Mollivirus kamchatka, a close relative to M. sibericum, isolated from surface soil sampled on the bank of the Kronotsky River in Kamchatka, Russian Federation. This discovery confirms that molliviruses have not gone extinct and are at least present in a distant subarctic continental location. This modern isolate exhibits a nucleocytoplasmic replication cycle identical to that of M. sibericum Its spherical particle (0.6 μm in diameter) encloses a 648-kb GC-rich double-stranded DNA genome coding for 480 proteins, of which 61% are unique to these two molliviruses. The 461 homologous proteins are highly conserved (92% identical residues, on average), despite the presumed stasis of M. sibericum for the last 30,000 years. Selection pressure analyses show that most of these proteins contribute to virus fitness. The comparison of these first two molliviruses clarify their evolutionary relationship with the pandoraviruses, supporting their provisional classification in a distinct family, the Molliviridae, pending the eventual discovery of intermediary missing links better demonstrating their common ancestry.IMPORTANCE Virology has long been viewed through the prism of human, cattle, or plant diseases, leading to a largely incomplete picture of the viral world. The serendipitous discovery of the first giant virus visible under a light microscope (i.e., >0.3 μm in diameter), mimivirus, opened a new era of environmental virology, now incorporating protozoan-infecting viruses. Planet-wide isolation studies and metagenome analyses have shown the presence of giant viruses in most terrestrial and aquatic environments, including upper Pleistocene frozen soils. Those systematic surveys have led authors to propose several new distinct families, including the Mimiviridae, Marseilleviridae, Faustoviridae, Pandoraviridae, and Pithoviridae We now propose to introduce one additional family, the Molliviridae, following the description of M. kamchatka, the first modern relative of M. sibericum, previously isolated from 30,000-year-old arctic permafrost.

A Puzzling Anomaly in the 4-Mer Composition of the Giant Pandoravirus Genomes Reveals a Stringent New Evolutionary Selection Process.

Pandoraviridae is a rapidly growing family of giant viruses, all of which have been isolated using laboratory strains of Acanthamoeba The genomes of 10 distinct strains have been fully characterized, reaching up to 2.5 Mb in size. These double-stranded DNA genomes encode the largest of all known viral proteomes and are propagated in oblate virions that are among the largest ever described (1.2 μm long and 0.5 μm wide). The evolutionary origin of these atypical viruses is the object of numerous speculations. Applying the chaos game representation to the pandoravirus genome sequences, we discovered that the tetranucleotide (4-mer) "AGCT" is totally absent from the genomes of 2 strains (Pandoravirus dulcis and Pandoravirus quercus) and strongly underrepresented in others. Given the amazingly low probability of such an observation in the corresponding randomized sequences, we investigated its biological significance through a comprehensive study of the 4-mer compositions of all viral genomes. Our results indicate that AGCT was specifically eliminated during the evolution of the Pandoraviridae and that none of the previously proposed host-virus antagonistic relationships could explain this phenomenon. Unlike the three other families of giant viruses (Mimiviridae, Pithoviridae, and Molliviridae) infecting the same Acanthamoeba host, the pandoraviruses exhibit a puzzling genomic anomaly suggesting a highly specific DNA editing in response to a new kind of strong evolutionary pressure.IMPORTANCE Recent years have seen the discovery of several families of giant DNA viruses infecting the ubiquitous amoebozoa of the genus Acanthamoeba With double-stranded DNA (dsDNA) genomes reaching 2.5 Mb in length packaged in oblate particles the size of a bacterium, the pandoraviruses are currently the most complex and largest viruses known. In addition to their spectacular dimensions, the pandoraviruses encode the largest proportion of proteins without homologs in other organisms, which is thought to result from a de novo gene creation process. While using comparative genomics to investigate the evolutionary forces responsible for the emergence of such an unusual giant virus family, we discovered a unique bias in the tetranucleotide composition of the pandoravirus genomes that can result only from an undescribed evolutionary process not encountered in any other microorganism.

Degenerate PCR Primers to Reveal the Diversity of Giant Viruses in Coastal Waters.

“Megaviridae” is a proposed family of giant viruses infecting unicellular eukaryotes. These viruses are ubiquitous in the sea and have impact on marine microbial community structure and dynamics through their lytic infection cycle. However, their diversity and biogeography have been poorly characterized due to the scarce detection of Megaviridae sequences in metagenomes, as well as the limitation of reference sequences used to design specific primers for this viral group. Here, we propose a set of 82 degenerated primers (referred to as MEGAPRIMER), targeting DNA polymerase genes (polBs) of Megaviridae. MEGAPRIMER was designed based on 921 Megaviridae polBs from sequenced genomes and metagenomes. By applying this primer set to environmental DNA meta-barcoding of a coastal seawater sample, we report 5595 non-singleton operational taxonomic units (OTUs) of Megaviridae at 97% nucleotide sequence identity. The majority of the OTUs were found to form diverse clades, which were phylogenetically distantly related to known viruses such as Mimivirus. The Megaviridae OTUs detected in this study outnumber the giant virus OTUs identified in previous individual studies by more than an order of magnitude. Hence, MEGAPRIMER represents a useful tool to study the diversity of Megaviridae at the population level in natural environments.

A Phylogenomic Study of Acanthamoeba polyphaga Draft Genome Sequences Suggests Genetic Exchanges With Giant Viruses.

Acanthamoeba are ubiquitous phagocytes predominant in soil and water which can ingest many microbes. Giant viruses of amoebae are listed among the Acanthamoeba-resisting microorganisms. Their sympatric lifestyle within amoebae is suspected to promote lateral nucleotide sequence transfers. Some Acanthamoeba species have shown differences in their susceptibility to giant viruses. Until recently, only the genome of a single Acanthamoeba castellanii Neff was available. We analyzed the draft genome sequences of Acanthamoeba polyphaga through several approaches, including comparative genomics, phylogeny, and sequence networks, with the aim of detecting putative nucleotide sequence exchanges with giant viruses. We identified a putative sequence trafficking between this Acanthamoeba species and giant viruses, with 366 genes best matching with viral genes. Among viruses, Pandoraviruses provided the greatest number of best hits with 117 (32%) for A. polyphaga. Then, genes from mimiviruses, Mollivirus sibericum, marseilleviruses, and Pithovirus sibericum were best hits in 67 (18%), 35 (9%), 24 (7%), and 2 (0.5%) cases, respectively. Phylogenetic reconstructions showed in a few cases that the most parsimonious evolutionary scenarios were a transfer of gene sequences from giant viruses to A. polyphaga. Nevertheless, in most cases, phylogenies were inconclusive regarding the sense of the sequence flow. The number and nature of putative nucleotide sequence transfers between A. polyphaga, and A. castellanii ATCC 50370 on the one hand, and pandoraviruses, mimiviruses and marseilleviruses on the other hand were analyzed. The results showed a lower number of differences within the same giant viral family compared to between different giant virus families. The evolution of 10 scaffolds that were identified among the 14 Acanthamoeba sp. draft genome sequences and that harbored ≥ 3 genes best matching with viruses showed a conservation of these scaffolds and their 46 viral genes in A. polyphaga, A. castellanii ATCC 50370 and A. pearcei. In contrast, the number of conserved genes decreased for other Acanthamoeba species, and none of these 46 genes were present in three of them. Overall, this work opens up several potential avenues for future studies on the interactions between Acanthamoeba species and giant viruses.

The number of genes encoding repeat domain-containing proteins positively correlates with genome size in amoebal giant viruses.

Curiously, in viruses, the virion volume appears to be predominantly driven by genome length rather than the number of proteins it encodes or geometric constraints. With their large genome and giant particle size, amoebal viruses (AVs) are ideally suited to study the relationship between genome and virion size and explore the role of genome plasticity in their evolutionary success. Different genomic regions of AVs exhibit distinct genealogies. Although the vertically transferred core genes and their functions are universally conserved across the nucleocytoplasmic large DNA virus (NCLDV) families and are essential for their replication, the horizontally acquired genes are variable across families and are lineage-specific. When compared with other giant virus families, we observed a near–linear increase in the number of genes encoding repeat domain-containing proteins (RDCPs) with the increase in the genome size of AVs. From what is known about the functions of RDCPs in bacteria and eukaryotes and their prevalence in the AV genomes, we envisage important roles for RDCPs in the life cycle of AVs, their genome expansion, and plasticity. This observation also supports the evolution of AVs from a smaller viral ancestor by the acquisition of diverse gene families from the environment including RDCPs that might have helped in host adaption.

Crystal structures of two forms of the Acanthamoeba polyphaga mimivirus Rab GTPase.

Acanthamoeba polyphaga mimivirus (APMV) is a member of the family of giant viruses, harboring a 1,200 kbp genome within its 700 nm-diameter viral particle. The R214 gene of the APMV genome was recently shown to encode a homologue of the Rab GTPases, molecular switch proteins known to play a pivotal role in the regulation of membrane trafficking that were considered to exist only in eukaryotes. Herein, we report the first crystal structures of GDP- and GTP-bound forms of APMV Rab GTPase, both of which were determined at high resolution. An in-depth structural comparison of APMV Rab with each other and with mammalian Rab homologues led to an atomic-level elucidation of the inactive-active conformational change upon GDP/GTP exchange. APMV Rab GTPase exhibited considerable structural similarity to human Rab5, as previously predicted based on its amino acid sequence. However, it also contains unique structural features differentiating it from mammalian homologues, such as the functional substitution of a phenylalanine residue for the stabilization of the nucleotide's guanine base.

Giant viruses: update, enigmas, controversies and perspectives

Unlike microbes known in his time, the first virus (that of tobacco mosaic disease) was discovered by Ivanoski in 1892 because it was not retained by Chamberland's porcelain candles. For more than a century afterward, viruses were equated with this simple property that is still extensively used today (using modern 0,2 µm pore filters) as a practical criterion to delineate the "viral fraction" from other microbes in medical or environmental samples. The first documented exception to the simplistic criterion of particle size came with the discovery of Mimivirus, the viral nature of which was eventually recognized in 2003, following ten years during which it was mistaken for an obligate intracellular bacterium. Thirteen more years later, we now realize that non-filtering "giant viruses" are not rare, probably ubiquitous, and come in a large variety of virion shapes, genome sizes, gene contents, and replication strategies. Following a quick description of the 4 giant virus families known today, we discuss the enigmas, controversies and perspectives of conceptual revolutions that are brought about by this new and booming area of virology.

Giant Viruses of Amoebas: An Update.

During the 12 past years, five new or putative virus families encompassing several members, namely Mimiviridae, Marseilleviridae, pandoraviruses, faustoviruses, and virophages were described. In addition, Pithovirus sibericum and Mollivirus sibericum represent type strains of putative new giant virus families. All these viruses were isolated using amoebal coculture methods. These giant viruses were linked by phylogenomic analyses to other large DNA viruses. They were then proposed to be classified in a new viral order, the Megavirales, on the basis of their common origin, as shown by a set of ancestral genes encoding key viral functions, a common virion architecture, and shared major biological features including replication inside cytoplasmic factories. Megavirales is increasingly demonstrated to stand in the tree of life aside Bacteria, Archaea, and Eukarya, and the megavirus ancestor is suspected to be as ancient as cellular ancestors. In addition, giant amoebal viruses are visible under a light microscope and display many phenotypic and genomic features not found in other viruses, while they share other characteristics with parasitic microbes. Moreover, these organisms appear to be common inhabitants of our biosphere, and mimiviruses and marseilleviruses were isolated from human samples and associated to diseases. In the present review, we describe the main features and recent findings on these giant amoebal viruses and virophages.

Welcome to pandoraviruses at the 'Fourth TRUC' club.

Nucleocytoplasmic large DNA viruses, or representatives of the proposed order Megavirales, belong to families of giant viruses that infect a broad range of eukaryotic hosts. Megaviruses have been previously described to comprise a fourth monophylogenetic TRUC (things resisting uncompleted classification) together with cellular domains in the universal tree of life. Recently described pandoraviruses have large (1.9–2.5 MB) and highly divergent genomes. In the present study, we updated the classification of pandoraviruses and other reported giant viruses. Phylogenetic trees were constructed based on six informational genes. Hierarchical clustering was performed based on a set of informational genes from Megavirales members and cellular organisms. Homologous sequences were selected from cellular organisms using TimeTree software, comprising comprehensive, and representative sets of members from Bacteria, Archaea, and Eukarya. Phylogenetic analyses based on three conserved core genes clustered pandoraviruses with phycodnaviruses, exhibiting their close relatedness. Additionally, hierarchical clustering analyses based on informational genes grouped pandoraviruses with Megavirales members as a super group distinct from cellular organisms. Thus, the analyses based on core conserved genes revealed that pandoraviruses are new genuine members of the ‘Fourth TRUC’ club, encompassing distinct life forms compared with cellular organisms.

Complete genome sequence of Tunisvirus, a new member of the proposed family Marseilleviridae.

Marseillevirus is the founding member of the proposed family Marseilleviridae, which is the second discovered family of giant viruses that infect amoebae. These viruses have been recovered from environmental water samples and, more recently, from humans. Tunisvirus was isolated from fountain water in Tunis, Tunisia, by culturing on Acanthamoeba spp. and is a new marseillevirus. We describe here its 380,011 base-pair genome. A total of 484 proteins were identified, among which 320 and 358 have an ortholog in Marseillevirus and Lausannevirus (e-value<1e-2), respectively, and 259 and 299 have best reciprocal hits with a Marseillevirus and a Lausannevirus protein, respectively. In addition, a significant hit was found in organisms other than marseilleviruses for 144 Tunisvirus proteins, indicating extensive lateral gene transfers, as has been demonstrated previously for Marseillevirus. Finally, a total of 21 ORFans were identified. Phylogeny reconstructions and analysis of the gene repertoires of marseilleviruses, including the proportion of orthologs and the mean amino acid identity between genes in pairs, suggest that the proposed family Marseilleviridae encompasses three lineages. Lineage A is composed of Marseillevirus, Cannes 8 virus and Senegalvirus; lineage B is represented by Lausannevirus alone; and lineage C has Tunisvirus as its first member. Taken together, these findings suggest that the marseilleviruses display a substantial level of diversity.

Pandoraviruses are highly derived phycodnaviruses

The recently discovered Pandoraviruses are by far the largest viruses known, with their 2 megabase genomes exceeding in size the genomes of numerous bacteria and archaea. Pandoraviruses show a distant relationship with other nucleocytoplasmic large DNA viruses (NCLDV) of eukaryotes, lack some of the NCLDV core genes and in particular do not appear to be specifically related to the other, better characterized family of giant viruses, the Mimiviridae. Here we report phylogenetic analysis of 6 core NCLDV genes that confidently places Pandoraviruses within the family Phycodnaviridae, with an apparent specific affinity with Coccolithoviruses. We conclude that, despite their many unusual characteristics, Pandoraviruses are highly derived phycodnaviruses. These findings imply that giant viruses have independently evolved from smaller NCLDV on at least two occasions.This article was reviewed by Patrick Forterre and Lakshminarayan Iyer. For the full reviews, see the Reviewers’ reports section.

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

BackgroundThe family Mimiviridae belongs to the large monophyletic group of Nucleo-Cytoplasmic Large DNA Viruses (NCLDV; proposed order Megavirales) and encompasses giant viruses infecting amoeba and probably other unicellular eukaryotes. The recent discovery of the Cafeteria roenbergensis virus (CroV), a distant relative of the prototype mimiviruses, led to a substantial expansion of the genetic variance within the family Mimiviridae. In the light of these findings, a reassessment of the relationships between the mimiviruses and other NCLDV and reconstruction of the evolution of giant virus genomes emerge as interesting and timely goals.ResultsDatabase searches for the protein sequences encoded in the genomes of several viruses originally classified as members of the family Phycodnaviridae, in particular Organic Lake phycodnaviruses and Phaeocystis globosa viruses (OLPG), revealed a greater number of highly similar homologs in members of the Mimiviridae than in phycodnaviruses. We constructed a collection of 898 Clusters of Orthologous Genes for the putative expanded family Mimiviridae (MimiCOGs) and used these clusters for a comprehensive phylogenetic analysis of the genes that are conserved in most of the NCLDV. The topologies of the phylogenetic trees for these conserved viral genes strongly support the monophyly of the OLPG and the mimiviruses. The same tree topology was obtained by analysis of the phyletic patterns of conserved viral genes. We further employed the mimiCOGs to obtain a maximum likelihood reconstruction of the history of genes losses and gains among the giant viruses. The results reveal massive gene gain in the mimivirus branch and modest gene gain in the OLPG branch.ConclusionsThese phylogenomic results reported here suggest a substantial expansion of the family Mimiviridae. The proposed expanded family encompasses a greater diversity of viruses including a group of viruses with much smaller genomes than those of the original members of the Mimiviridae. If the OLPG group is included in an expanded family Mimiviridae, it becomes the only family of giant viruses currently shown to host virophages. The mimiCOGs are expected to become a key resource for phylogenomics of giant viruses.

Translation in Giant Viruses: A Unique Mixture of Bacterial and Eukaryotic Termination Schemes

Mimivirus and Megavirus are the best characterized representatives of an expanding new family of giant viruses infecting Acanthamoeba. Their most distinctive features, megabase-sized genomes carried in particles of size comparable to that of small bacteria, fill the gap between the viral and cellular worlds. These giant viruses are also uniquely equipped with genes coding for central components of the translation apparatus. The presence of those genes, thought to be hallmarks of cellular organisms, revived fundamental interrogations on the evolutionary origin of these viruses and the link they might have with the emergence of eukaryotes. In this work, we focused on the Mimivirus-encoded translation termination factor gene, the detailed primary structure of which was elucidated using computational and experimental approaches. We demonstrated that the translation of this protein proceeds through two internal stop codons via two distinct recoding events: a frameshift and a readthrough, the combined occurrence of which is unique to these viruses. Unexpectedly, the viral gene carries an autoregulatory mechanism exclusively encountered in bacterial termination factors, though the viral sequence is related to the eukaryotic/archaeal class-I release factors. This finding is a hint that the virally-encoded translation functions may not be strictly redundant with the one provided by the host. Lastly, the perplexing occurrence of a bacterial-like regulatory mechanism in a eukaryotic/archaeal homologous gene is yet another oddity brought about by the study of giant viruses.