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Review

Reclassification of Giant Viruses Composing a Fourth Domain of Life in the New Order Megavirales

Colson P.a, b · de Lamballerie X.b, c · Fournous G.a · Raoult D.a, b

Author affiliations

aAix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), CNRS UMR 6236 – IRD 198 – INSERM 1095, Méditerranée Infection, Facultés de Médecine et de Pharmacie, bPôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance publique des hôpitaux de Marseille, et cUnité des Virus Emergents, UMR190 Emergence des pathologies virales, Aix-Marseille Université, Institut de Recherche pour le Développement, EHSP French School of Public Health, Faculté de Médecine, Marseille, France

Corresponding Author

Prof. Didier Raoult, MD, PhD

Unité des Rickettsies, URMITE UMR CNRS 6236 IRD 198

Faculté de Médecine, Aix-Marseille Université

27 Boulevard Jean Moulin, FR–13385 Marseille Cedex 05 (France)

Tel. +33 491 324 375, E-Mail didier.raoult@gmail.com

Related Articles for ""

Intervirology 2012;55:321–332

Abstract

Interest in giant viruses has risen sharply since 2003, following the discovery of the Mimivirus and four other protist-infecting giant viruses that are linked to the nucleocytoplasmic large DNA viruses (NCLDVs). Despite considerable heterogeneity in hosts and genome sizes, the NCLDVs have been shown to be monophyletic based on analyses of their sequences and gene repertoires and recent studies have proposed that these viruses share a common ancient ancestor and compose a fourth domain of life. In addition, several characteristics of these giant viruses contradict or do not match the criteria used for the canonical definition of viruses, and the NCLDV denomination is not completely appropriate. We propose here to define a new viral order named Megavirales.

© 2012 S. Karger AG, Basel


Keywords

Megavirales · Giant virus · Acanthamoeba polyphaga Mimivirus · Mimiviridae · Nucleocytoplasmic large DNA viruses · Amoeba · Acanthamoeba spp. · Phagocytic protist · Classification · Domains of life ·


Introduction

The existence of viruses with singularly large particle and genome sizes has been appreciated since the discovery of jumbo bacteriophages in the 1970s and the phycodnaviruses in the early 1980s [1,2]. The interest in giant viruses increased dramatically in 2003 with the discovery of Acanthamoeba polyphaga Mimivirus, whose genome was the largest ever described among viruses (1,181 kb). It encodes more than 900 proteins, including some never identified previously in viruses [3,4]. Overall, the Mimivirus discovery has led to considerable breakthroughs in our understanding of the definition, origin, and evolution of viruses [4,5,6,7]. Consequently, the number of publications and citations related to giant viruses has increased by more than 1 log (online suppl. fig. S1; for all online suppl. material, see www.karger.com?doi=10.1159/000336562). Since 2008, several new giant viruses including close relatives to Mimivirus (Mamavirus, Terra2, Moumou, Courdo 11, Megavirus chilensis) and others more distantly related (Cafeteria roenbergensis virus (CroV), Marseillevirus, and Lausannevirus) have been recovered from different phagocytic protists and water samples by four teams (table 1; online suppl. table S1; fig. 1a) [5,8,9,10,11,12,13,14].

Table 1

Main features of nucleocytoplasmic large DNA viruses whose genome is available in the NCBI GenBank genome database

http://www.karger.com/WebMaterial/ShowPic/196869

Fig. 1

Phylogeny reconstruction from a cured concatenated alignment of universal NCVOGs [including primase-helicase (NCVOG0023), DNA polymerase (NCVOG0038), packaging ATPase (NCVOG0249), and A2L-like transcription factor (NCVOG0262)] for the giant viruses currently classified as NCLDVs (a) [modified from [14]] and the Mimiviridae (b). Probabilities are mentioned near branches as a percentage and are used as confidence values of tree branches. Only probabilities at major nodes are shown. Scale bar represents the number of estimated changes per position for a unit of branch length.

http://www.karger.com/WebMaterial/ShowPic/196865

All of the previously mentioned protist-associated giant viruses have been linked to nucleocytoplasmic large DNA viruses (NCLDVs) (tables 1, 2, 3, 4) [15,16,17,18]. However, this grouping is not completely appropriate and several unique features of the NCLDVs do not match the criteria for the canonical definition of viruses [6,32,33]. In addition, these giant viruses were suggested to share a common ancestral origin and compose a new domain of life, aside Bacteria, Archaea, and Eukarya [17,18,34]. Therefore, we propose here to define a new viral order named Megavirales.

Table 2

Brief description of the main features of NCLDVs

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Table 3

A brief history of key steps in the definition of the NCLDV superfamily and the Megavirales order

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Table 4

Range of genome sizes, % GC content, coding proportions of genomes, and numbers of genes for the seven nucleocytoplasmic large DNA virus family members whose genome sequences are available in the NCBI GenBank genome database

http://www.karger.com/WebMaterial/ShowPic/196866

Rationale and Argument Supporting the Definition of a New Viral Order

The Current Definition and Classification of Giant Viruses Are Inappropriate

The canonical definition of viruses was described by Lwoff [33] during the pregenomic era in 1957 and was historically based on negative criteria (online suppl. table S2). Later, genomics failed to identify any common gene in the virosphere that could be equivalent to universal proteins or ribosomal RNA for Eukarya, Archaea, and Bacteria[6,35,36,37]. Thus, viruses remained separate from these biological entities. Recently, a new classification was proposed, which defines them as capsid-encoding organisms as opposed to ribosome-encoding organisms that compose the three canonical domains of life and are used to complete the viral life cycle (fig. 2). Besides, major monophyletic classes of viruses were tentatively defined [ [15,37]. Most giant viruses were linked to one of these classes, NCLDV, which includes Poxviridae, Asfarviridae, Iridoviridae, Ascoviridae, Phycodnaviridae, Mimiviridae, and Marseilleviridae (Marseillevirus and Lausannevirus) (tables 1, 2, 3; fig. 1a; online suppl. table S1) [13,17]. Regarding Mimiviridae, new giant viruses infecting amoebae have been described by La Scola et al. [9 ]in 2010 and phylogeny reconstructions based on highly conserved genes enable delineating three lineages, referred to as A, B, and C. One of these lineages (A) is composed of Mimivirus and closely related viruses (table 1; fig. 1b). The recently described Megavirus chilensis[10] is closely related to a giant virus previously recovered and classified within lineage C (table 1; fig. 1b). CroV has been also classified among the Mimiviridae, apart from the group composed by the lineages A, B, and C (table 1; fig. 1b) [11,14].

Fig. 2

Schematic illustrating the relationships between ribosome-encoding organisms and capsid-encoding organisms, including the Megavirales members.

http://www.karger.com/WebMaterial/ShowPic/196864

Despite large heterogeneity in their hosts and genome sizes, the monophyly of the NCLDVs has been attested by phylogenetic and phyletic analyses, and the gene repertoires of these viruses distinguished them from bacteria, archaea, and eukaryotes [15,18,37]. The NCLDVs were originally defined as sharing nine genes found in all families, including three viral hallmark genes (table 3) [15]. Later, Yutin et al. [17] identified a set of 1,445 NCLDV clusters of orthologous groups of proteins, referred to as NCVOGs, that included 177 represented in two or more NCLDV families and 5 present in all viruses. Other viruses, including Myoviridae, Nimaviridae, Herpesviridae, and Polydnaviridae, exhibit large genome and particle sizes, but their gene content precludes their incorporation within the NCLDVs [15,37]. Some viral hallmark genes are shared between the NCLDVs and other large DNA viruses, as exemplified by the B-family DNA polymerases that are shared with herpesviruses and baculoviruses, but there are considerable numbers of other genes shared by the NCLDVs to the exclusion of all other large viruses [17,37]. Moreover, the DNA replication and transcription of herpesviruses and baculoviruses occur exclusively in the nucleus, in contrast to NCLDVs [15]. Regarding Myoviridae, they are tailed bacteriophages [28].

Based on current knowledge, giant viruses and other canonical viruses differ in many aspects, which is not consistent with the concept (conveyed by Lwoff’s classification) that the viral world is a homogeneous class of entities (online suppl. table S2) [6,16,32]. As an example, the huge gap between the Mimivirus and the hepatitis C virus is striking. The specific NCLDV features that strongly challenge the canonical definition of viruses are listed below (online suppl. table S2).

The NCLDVs have a capsid diameter that ranges between 150 and 500 nm, which contradicts the historical concept of viruses as small, ultrafilterable entities [32,38,39,40]. In addition, the NCLDVs have large genomes that range in size between 103 and 1,259 kb and harbor 95–1,120 genes (table 4).

Viral messenger RNAs were detected in Mimivirus and Marseillevirus particles [4,12]. These transcripts encode notably for capsid protein, DNA polymerase, or TFII-like transcription factor. The presence of RNA in the vaccinia virus particles has also been reported [41]. This contradicts a key point of Lwoff’s viral classification, which stated that viruses only harbor one type of nucleic acid [32,33].

The Mimiviridae and Marseilleviridae genomes encode proteins involved in translation, which represents a unique feature of these viruses [4,12,32]. Besides, the genomes of Mimiviridae and Phycodnaviridae exhibit tRNAs [4,28].

The NCLDVs were suggested to have a common ancestral origin dating back to an early stage of Eukarya evolution (table 3) [15,17,34,37]. Thus, Yutin et al. [17 ]used maximum-likelihood reconstruction to delineate a set of 47 conserved genes that were probably present in the genome of the NCLDV common ancestor, which may have been a giant virus (fig. 3). Additionally, the NCLDVs infect a considerable diversity of hosts that belong to the three canonical domains of life [17,28,42]. Moreover, cross-mapping of the NCLDV and host eukaryotic trees generated a complex network in which members of the same NCLDV branch exhibited relationships with eukaryotic organisms of different supergroups [17]. For example, despite the relationship between them, irido-/ascoviruses infect animals, while Marseillevirus infects a protist. Yutin et al. [17] have proposed the hypothesis of a ‘Big Bang-like’ event concomitantly with eukaryogenesis for the origin of the NCLDVs [43].

Fig. 3

Functional annotation and probable origin of the reconstructed core gene set of the common ancestor of the NCLDVs (47 NCVOGs) [adapted from [18]].

http://www.karger.com/WebMaterial/ShowPic/196863

Furthermore, it was proposed in 2010 that NCLDVs might define a fourth domain of life. This has been based on phylogenetic and phyletic studies of the repertoires of genes involved in information storage and processing and nucleotide transport and metabolism, and shared by Eukarya, Bacteria, Archaea, and the NCLDVs [34]. This work provided additional data supporting the monophyly and common origin of these giant viruses. In addition, it supports the hypotheses that the core genome of the NCLDVs may be as ancient as those of the three current canonical domains of life and that NCLDVs may have emerged as ancient roots from the rhizome of life [34,44]. It was claimed in a recent work that the methodology used by Boyer et al. [34] for phylogenetic reconstructions was not the most appropriate to avoid spurious tree topologies generated by compositional heterogeneity and homoplasy, and alternative informational gene phylogenies did not support a fourth domain of life for NCLDVs [45]. Nevertheless, these trees fail to show a monophyly of Eukarya as well. In addition, other recent findings based on extensive analysis of metagenomic data suggest the existence of domains other than Eukarya, Archaea, and Bacteria[46].

Other Major Features of Giant Viruses Classified Along with NCLDVs

The NCLDVs can be characterized by other peculiar features in addition to those that radically classify them as separate from other viruses.

Poxviridae, Iridoviridae, and Asfarviridae can build viral factories [47], also reported in the case of Mimivirus, Megavirus, Marseillevirus, and Lausannevirus [10,12,13,48]. These factories are associated with a massive production of virions.

The NCLDVs display a high level of genomic plasticity. Indeed, lineage-specific gene expansion and horizontal gene transfer have played a major role in the shaping of their genomes [4,42,49,50,51,52,53]. The proportion of duplicated genes in these viruses was found to range between 8 and 44%, with the highest proportions observed in Mimivirus [50,51]. In addition, horizontal gene transfer has generated considerable genome plasticity and mosaicism, although the direction or source of the transfers and the fraction of gene content involved remain controversial [7,51]. According to Filée [51], 0.8–11.9% of the genes were exchanged with the viral hosts, with the highest proportion being observed in Poxviridae, and up to 9.6% of the gene content was exchanged with bacteria, with the highest proportion being in Mimivirus. The potential mechanisms by which Poxviridae shape their genome through transfers of genes of host or viral origin have been particularly described [54,55,56,57]. In addition, the numbers of gene transfers with bacteria are the greatest for the Mimiviruses, Marseilleviruses, and phycodnaviruses that infect hosts feeding on bacteria [42]. The sympatric lifestyle within a phagocytic protist that grazes on bacteria, giant viruses, and virophages provides many opportunities indeed for these pathogens to gain and exchange genes. Thus, amoebae have been described as hot spots for gene transfer that may lead to the emergence of chimeric viruses and even the creation of new species [12,58]. Interestingly, a reduction in genome size by approximately 16% was recently observed for the Mimivirus when subcultured 150 times in a germ-free amoebal host [59].

In addition to the core gene set, NCLDV genomes contain open reading frames (ORFs) without detectable homologs, also known as ORFans [60]. Strikingly, 2.8–75.2% of ORFs in the NCLDV genomes lack homologs in the NCBI GenBank reference protein sequence database. Moreover, 0.3–10.4% of these ORFs have homologs in the GenBank environmental protein sequence database.

The NCLDVs themselves can be infected by viruses [61], as has been previously shown for eukaryotes, bacteria, and archaea. In 2008, La Scola et al. [5] identified Sputnik, a virus infecting Mamavirus, which led to the creation of the virophage concept. Since then three new virophages have been described in association with Mimiviridae and Phycodnaviridae [9,35,62]. Importantly, virophages may be involved in gene transfer [5,35].

Giant Viruses Classified with the NCLDVs Are Probably Common Inhabitants of Our Biosphere

According to our current knowledge, the NCLDVs remain a minority in the virosphere. Nevertheless, several findings indicate that they are common inhabitants of our biosphere. It is noteworthy that their presence has probably been largely underestimated up to this point because most metagenomic studies have adhered to the dogma of the small size of viruses by filtering samples prior to analysis (fig. 4) [63,64,65]. Notwithstanding, sequences similar to those from Mimivirus, African swine fever virus, and iridoviruses have already been identified in marine environmental samples or human serum and sewage [66,67,68,69,70,71]. Furthermore, giant viruses have been recovered from five different geographical areas worldwide and they have been isolated from approximately 20% of water samples in one study by optimizing amoebal culture protocols [9].

Fig. 4

Schematic illustrating how the giant viruses may have been excluded during the assessment of viromes by metagenomic studies that have filtered samples prior to analysis. Such procedures are inevitably preventing the detection of viruses larger than the pores of the filters used, i.e. 0.2–0.45 µm.

http://www.karger.com/WebMaterial/ShowPic/196862

NCLDV Is Not an Appropriate Denomination and Has No Recognized Taxonomic Meaning

Finally, the NCLDV denomination does not take into account that Mimivirus and Marseillevirus harbor both DNA and RNA. Moreover, the NCLDVs compose a superfamily, a grouping that has no formally recognized taxonomic meaning according to the International Committee on Taxonomy of Viruses (ICTV) (http://www. ictvonline.org/virusTaxonomy.asp?bhcp=1). In the current ICTV classification, none of the NCLDV families are assigned to a viral order. We propose that these viruses should be assigned to a newly defined order (a group of families sharing certain common characteristics according to the ICTV) named Megavirales, in reference to the uncommon size of both the members’ particles and their genomes.

Definition of the Megavirales

Viral members of the new Megavirales order correspond to the giant viruses previously classified within the NCLDVs (table 1; online suppl. table S1). Megavirales can be defined by the criteria mentioned below, as illustrated in figure 5.

Fig. 5

Major features of Megavirales members and criteria required for membership in the Megavirales order.

http://www.karger.com/WebMaterial/ShowPic/196861

All of the following single characteristics are required for membership in the order (the monothetical system [72]):

• Giant viral particle and genome, capsid diameter >150 nm and genome size >100 kb (or in that order of magnitude).

• Presence in the gene content of all nine class I NCLDV core genes, i.e. VV D5-type ATPase (superfamily III helicase), DNA polymerase (B family), VV A32 virion packaging ATPase, VV A18 helicase (superfamily II), capsid protein D13L, thiol oxidoreductase, VV D6R/D11L-like helicase (superfamily II), S/T protein kinase, transcription factor VLTF2 [15] and all five NCVOGs found in all NCLDVs (i.e. NCLDV major capsid protein, D5-like helicase-primase, DNA polymerase elongation subunit family B, A32-like packaging ATPase and Poxvirus Late Transcription Factor VLTF3-like) [18]. These genes have various functions and origins.

• Common ancestral origin and membership in the proposed fourth domain of life.

• A jelly-roll capsid protein, which is a hallmark viral protein [6,37]. The capsid is icosahedral in all NCLDVs except in poxviruses, where it forms intermediate structures during virion morphogenesis, but is not a protein of the virion [37,73].

Different combinations of properties among those listed above are required for membership in the order (the polythetical system): presence of both DNA and RNA; presence of proteins involved in the translation apparatus; substantial proportions of genes duplicated and involved in horizontal gene transfer within the genome; substantial proportions of ORFans and metaORFans among the gene repertoire; presence of viral factories; some or all steps of DNA replication and transcription occurring in the host cytoplasm, and possible infection by a virophage.

Conclusion

The tremendous recent increase in knowledge about giant viruses has generated divergence rather than reinforced the borders of the previously defined viral world. Megavirales gather viral entities that appear to be incompatible within the framework of the virosphere as it has been defined since the beginning of virology. Moreover, they lay the foundation for a new understanding in which viruses consolidate their status as early protagonists in evolution.


References

  1. Donelli G, Dore E, Frontali C, Grandolfo ME: Structure and physico-chemical properties of bacteriophage G. III. A homogeneous DNA of molecular weight 5 times 10(8). J Mol Biol 1975;94:555–565.
  2. Van Etten JL, Meints RH, Kuczmarski D, Burbank DE, Lee K: Viruses of symbiotic Chlorella-like algae isolated from Paramecium bursaria and Hydra viridis. Proc Natl Acad Sci USA 1982;79:3867–3871.
  3. La Scola B, Audic S, Robert C, Jungang L, de Lamballerie X, Drancourt M, Birtles R, Claverie JM, Raoult D: A giant virus in amoebae. Science 2003;299:2033.
  4. Raoult D, Audic S, Robert C, Abergel C, Renesto P, Ogata H, La Scola B, Suzan M, Claverie JM: The 1.2-megabase genome sequence of Mimivirus. Science 2004;306:1344–1350.
  5. La Scola B, Desnues C, Pagnier I, Robert C, Barrassi L, Fournous G, Merchat M, Suzan-Monti M, Forterre P, Koonin E, et al: The virophage as a unique parasite of the giant mimivirus. Nature 2008;455:100–104.
  6. Raoult D, Forterre P: Redefining viruses: lessons from Mimivirus. Nat Rev Microbiol 2008;6:315–319.
  7. Forterre P: Giant viruses: conflicts in revisiting the virus concept. Intervirology 2010;53:362–378.
  8. Colson P, Yutin N, Shabalina S, Robert C, Fournous G, La Scola B, Raoult D, Koonin EV: Viruses with over 1,000 genes: Acanthamoeba castellanii Mamavirus, a new mimivirus strain, and reannotation of Mimivirus genes. Genome Biol Evol 2011;3:737–742.
  9. La Scola B, Campocasso A, N’Dong R, Fournous G, Barrassi L, Flaudrops C, Raoult D: Tentative characterization of new environmental giant viruses by MALDI-TOF mass spectrometry. Intervirology 2010;53:344–353.
  10. Arslan D, Legendre M, Seltzer V, Abergel C, Claverie JM: Distant Mimivirus relative with a larger genome highlights the fundamental features of Megaviridae. Proc Natl Acad Sci USA 2011;108:17486–17491.
  11. Fischer MG, Allen MJ, Wilson WH, Suttle CA: Giant virus with a remarkable complement of genes infects marine zooplankton. Proc Natl Acad Sci USA 2010;107:19508–19513.
  12. Boyer M, Yutin N, Pagnier I, Barrassi L, Fournous G, Espinosa L, Robert C, Azza S, Sun S, Rossmann MG, et al: Giant Marseillevirus highlights the role of amoebae as a melting pot in emergence of chimeric microorganisms. Proc Natl Acad Sci USA 2009;106:21848–21853.
  13. Thomas V, Bertelli C, Collyn F, Casson N, Telenti A, Goesmann A, Croxatto A, Greub G: Lausannevirus, a giant amoebal virus encoding histone doublets. Environ Microbiol 2011;13:1454–1466.
  14. Colson P, Gimenez G, Boyer M, Fournous G, Raoult D: The giant Cafeteria roenbergensis virus that infects a widespread marine phagocytic protist is a new member of the fourth domain of Life. PLoS One 2011;6:e18935.
  15. Iyer LM, Aravind L, Koonin EV: Common origin of four diverse families of large eukaryotic DNA viruses. J Virol 2001;75:11720–11734.
  16. Iyer LM, Balaji S, Koonin EV, Aravind L: Evolutionary genomics of nucleo-cytoplasmic large DNA viruses. Virus Res 2006;117:156–184.
  17. Yutin N, Wolf YI, Raoult D, Koonin EV: Eukaryotic large nucleo-cytoplasmic DNA viruses: clusters of orthologous genes and reconstruction of viral genome evolution. Virol J 2009;6:223.
  18. Koonin EV, Yutin N: Origin and evolution of eukaryotic large nucleo-cytoplasmic DNA viruses. Intervirology 2010;53:284–292.
  19. Lefkowitz EJ, Wang C, Upton C: Poxviruses: past, present and future. Virus Res 2006;117:105–118.
  20. Baroudy BM, Venkatesan S, Moss B: Incompletely base-paired flip-flop terminal loops link the two DNA strands of the vaccinia virus genome into one uninterrupted polynucleotide chain. Cell 1982;28:315–324.
  21. Williams T: The iridoviruses. Adv Virus Res 1996;46:345–412.
  22. Jakob NJ, Müller K, Bahr U, Darai G: Analysis of the first complete DNA sequence of an invertebrate iridovirus: coding strategy of the genome of Chilo iridescent virus. Virology 2001;286:182–196.
  23. Federici BA: Enveloped double-stranded DNA insect virus with novel structure and cytopathology. Proc Natl Acad Sci USA 1983;80:7664–7668.
  24. Federici BA, Vlak JM, Hamm JJ: Comparative study of virion structure, protein composition and genomic DNA of three ascovirus isolates. J Gen Virol 1990;71:1661–1668.
  25. Dixon LK, Abrams CC, Bowick G, Goatley LC, Kay-Jackson PC, Chapman D, Liverani E, Nix R, Silk R, Zhang F: African swine fever virus proteins involved in evading host defence systems. Vet Immunol Immunopathol 2004;100:117–134.
  26. de Villiers EP, Gallardo C, Arias M, da Silva M, Upton C, Martin R, Bishop RP: Phylogenomic analysis of 11 complete African swine fever virus genome sequences. Virology 2010;400:128–136.
  27. Wilson WH, Van Etten JL, Allen MJ: The Phycodnaviridae: the story of how tiny giants rule the world. Curr Top Microbiol Immunol 2009;328:1–42.
  28. Van Etten JL, Lane LC, Dunigan DD: DNA viruses: the really big ones giruses). Annu Rev Microbiol 2010;64:83–99.
  29. Van Etten JL: Unusual life style of giant chlorella viruses. Annu Rev Genet 2003;37:153–195.
  30. Wilson WH, Schroeder DC, Allen MJ, Holden MT, Parkhill J, Barrell BG, Churcher C, Hamlin N, Mungall K, Norbertczak H, et al: Complete genome sequence and lytic phase transcription profile of a Coccolithovirus. Science 2005;309:1090–1092.
  31. Fuhrman JA: Marine viruses and their biogeochemical and ecological effects. Nature 1999;399:541–548.
  32. Raoult D, La Scola B, Birtles R: The discovery and characterization of Mimivirus, the largest known virus and putative pneumonia agent. Clin Infect Dis 2007;45:95–102.
  33. Lwoff A: The concept of virus. J Gen Microbiol 1957;17:239–253.
  34. Boyer M, Madoui M-A, Gimenez G, La Scola B, Raoult D: Phylogenetic and phyletic studies of informational genes in genomes highlight existence of a 4th domain of life including giant viruses. PloS One 2010;5:e15530.
  35. Fischer MG, Suttle CA: A virophage at the origin of large DNA transposons. Science 2011;332:231–234.
  36. Woese CR, Kandler O, Wheelis ML: Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proc Natl Acad Sci USA 1990;87:4576–4579.
  37. Koonin EV, Senkevich TG, Dolja VV: The ancient virus world and evolution of cells. Biol Direct 2006;1:29.
  38. Ivanovski D: Über die Mosaikkrankheit der Tabakspflanze. St Petersb Acad Imp Sci Bull 1892;35:67–70.
  39. Beijerinck MW: Über ein Contagium vivum fluidum als Ursache der Fleckenkrankheit der Tabaksblätter. Verhandelingen der Koninklyke akademie van Wettenschappen te Amsterdam; in Johnson J (ed): Phytopathological Classics No 7. St Paul, American Phytopathological Society, 1942, pp 33–52.
  40. Lustig A, Levine AJ: One hundred years of virology. J Virol 1992;66:4629–4631.
  41. Roening G, Holowczak JA: Evidence for the presence of RNA in the purified virions of vaccinia virus. J Virol 1974;14:704–708.
  42. Filée J, Chandler M: Gene exchange and the origin of giant viruses. Intervirology 2010;53:354–361.
  43. Koonin EV, Wolf YI, Nagasaki K, Dolja VV: The Big Bang of picorna-like virus evolution antedates the radiation of eukaryotic supergroups. Nat Rev Microbiol 2008;6:925–939.
  44. Raoult D: The post-Darwinist rhizome of life. Lancet 2010;375:104–105.
  45. Williams TA, Embley TM, Heinz E: Informational gene phylogenies do not support a fourth domain of life for nucleocytoplasmic large DNA viruses. PLoS One 2011;6:e21080.
  46. Wu D, Wu M, Halpern A, Rusch DB, Yooseph S, Frazier M, Venter JC, Eisen JA: Stalking the fourth domain in metagenomic data: searching for, discovering, and interpreting novel, deep branches in marker gene phylogenetic trees. PLoS One 2011;6:e18011.
  47. Novoa RR, Calderita G, Arranz R, Fontana J, Granzow H, Risco C: Virus factories: associations of cell organelles for viral replication and morphogenesis. Biol Cell 2005;97:147–172.
  48. Suzan-Monti M, La Scola B, Barrassi L, Espinosa L, Raoult D: Ultrastructural characterization of the giant volcano-like virus factory of Acanthamoeba polyphaga Mimivirus. PLoS One 2007;2:e328.
  49. Suzan-Monti M, La Scola B, Raoult D: Genomic and evolutionary aspects of Mimivirus. Virus Res 2006;117:145–155.
  50. Suhre K: Gene and genome duplication in Acanthamoeba polyphaga Mimivirus. J Virol 2005;79:14095–14101.
  51. Filée J: Lateral gene transfer, lineage-specific gene expansion and the evolution of nucleo-cytoplasmic large DNA viruses. J Invertebr Pathol 2009;101:169–171.
  52. Moreira D, Brochier-Armanet C: Giant viruses, giant chimeras: the multiple evolutionary histories of Mimivirus genes. BMC Evol Biol 2008;8:12.
  53. Colson P, Raoult D: Gene repertoire of amoeba-associated giant viruses. Intervirology 2010;53:330–343.
  54. Shackelton LA, Holmes EC: The evolution of large DNA viruses: combining genomic information of viruses and their hosts. Trends Microbiol 2004;12:458–465.
  55. McLysaght A, Baldi PF, Gaut BS: Extensive gene gain associated with adaptive evolution of poxviruses. Proc Natl Acad Sci USA 2003;100:15655–15660.
  56. Evans DH, Stuart D, McFadden G: High levels of genetic recombination among cotransfected plasmid DNAs in poxvirus-infected mammalian cells. J Virol 1988;62:367–375.
  57. Pickup DJ, Ink BS, Parsons BL, Hu W, Joklik WK: Spontaneous deletions and duplications of sequences in the genome of cowpox virus. Proc Natl Acad Sci USA 1984;81:6817–6821.
  58. Raoult D, Boyer M: Amoebae as genitors and reservoirs of giant viruses. Intervirology 2010;53:321–329.
  59. Boyer M, Azza S, Barrassi L, Klose T, Campocasso A, Pagnier I, Fournous G, Borg A, Robert C, Zhang X, et al: Mimivirus shows dramatic genome reduction after intra-amoebal culture. Proc Natl Acad Sci USA 2011;108:10296–10301.
  60. Boyer M, Gimenez G, Suzan-Monti M, Raoult D: Classification and determination of possible origins of ORFans through analysis of nucleocytoplasmic large DNA viruses. Intervirology 2010;53:310–320.
  61. Desnues C, Boyer M, Raoult D: Sputnik, a virophage infecting the viral domain of life. Adv Vir Res 2012;82:63–89.
    External Resources
  62. Yau S, Lauro FM, Demaere MZ, Brown MV, Thomas T, Raftery MJ, Andrews-Pfannkoch C, Lewis M, Hoffman JM, Gibson JA, et al: Virophage control of antarctic algal host-virus dynamics. Proc Natl Acad Sci USA 2011;108:6163–6168.
  63. Edwards RA, Rohwer F: Viral metagenomics. Nat Rev Microbiol 2005;3:504–510.
  64. Angly FE, Willner D, Prieto-Davó A, Edwards RA, Schmieder R, Vega-Thurber R, Antonopoulos DA, Barott K, Cottrell MT, Desnues C, et al: The GAAS metagenomic tool and its estimations of viral and microbial average genome size in four major biomes. PLoS Comput Biol 2009;5:e1000593.
    External Resources
  65. Thurber RV, Haynes M, Breitbart M, Wegley L, Rohwer F: Laboratory procedures to generate viral metagenomes. Nat Protoc 2009;4:470–483.
  66. Ghedin E, Claverie JM: Mimivirus relatives in the Sargasso Sea. Virol J 2005;2:62.
  67. Rusch DB, Halpern AL, Sutton G, Heidelberg KB, Williamson S, Yooseph S, Wu D, Eisen JA, Hoffman JM, Remington K, et al: The Sorcerer II Global Ocean Sampling expedition: northwest Atlantic through eastern tropical Pacific. PLoS Biol 2007;5:e77.
    External Resources
  68. Monier A, Larsen JB, Sandaa RA, Bratbak G, Claverie JM, Ogata H: Marine mimivirus relatives are probably large algal viruses. Virol J 2008;5:12.
  69. Ogata H, Toyoda K, Tomaru Y, Nakayama N, Shirai Y, Claverie JM, Nagasaki K: Remarkable sequence similarity between the dinoflagellate-infecting marine girus and the terrestrial pathogen African swine fever virus. Virol J 2009;6:178.
  70. Loh J, Zhao G, Presti RM, Holtz LR, Finkbeiner SR, Droit L, Villasana Z, Todd C, Pipas JM, Calgua B, et al: Detection of novel sequences related to African swine fever virus in human serum and sewage. J Virol 2009;83:13019–13025.
  71. Kristensen DM, Mushegian AR, Dolja VV, Koonin EV: New dimensions of the virus world discovered through metagenomics. Trends Microbiol 2010;18:11–19.
  72. Condit RC: Principles of virology; in Knipe DM, Howley PM (eds): Fields Virology, ed 5, Philadelphia, Lippincott Williams & Wilkins, 2007.
  73. Moss B: Poxviridae: the viruses and their replication; in Fields BN, Knipe DM, Howley PM (eds): Fields Virology, ed 3. Philadelphia, Lippincott-Raven, 1996, pp 2637–2671.

Author Contacts

Prof. Didier Raoult, MD, PhD

Unité des Rickettsies, URMITE UMR CNRS 6236 IRD 198

Faculté de Médecine, Aix-Marseille Université

27 Boulevard Jean Moulin, FR–13385 Marseille Cedex 05 (France)

Tel. +33 491 324 375, E-Mail didier.raoult@gmail.com


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Published online: April 14, 2012
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References

  1. Donelli G, Dore E, Frontali C, Grandolfo ME: Structure and physico-chemical properties of bacteriophage G. III. A homogeneous DNA of molecular weight 5 times 10(8). J Mol Biol 1975;94:555–565.
  2. Van Etten JL, Meints RH, Kuczmarski D, Burbank DE, Lee K: Viruses of symbiotic Chlorella-like algae isolated from Paramecium bursaria and Hydra viridis. Proc Natl Acad Sci USA 1982;79:3867–3871.
  3. La Scola B, Audic S, Robert C, Jungang L, de Lamballerie X, Drancourt M, Birtles R, Claverie JM, Raoult D: A giant virus in amoebae. Science 2003;299:2033.
  4. Raoult D, Audic S, Robert C, Abergel C, Renesto P, Ogata H, La Scola B, Suzan M, Claverie JM: The 1.2-megabase genome sequence of Mimivirus. Science 2004;306:1344–1350.
  5. La Scola B, Desnues C, Pagnier I, Robert C, Barrassi L, Fournous G, Merchat M, Suzan-Monti M, Forterre P, Koonin E, et al: The virophage as a unique parasite of the giant mimivirus. Nature 2008;455:100–104.
  6. Raoult D, Forterre P: Redefining viruses: lessons from Mimivirus. Nat Rev Microbiol 2008;6:315–319.
  7. Forterre P: Giant viruses: conflicts in revisiting the virus concept. Intervirology 2010;53:362–378.
  8. Colson P, Yutin N, Shabalina S, Robert C, Fournous G, La Scola B, Raoult D, Koonin EV: Viruses with over 1,000 genes: Acanthamoeba castellanii Mamavirus, a new mimivirus strain, and reannotation of Mimivirus genes. Genome Biol Evol 2011;3:737–742.
  9. La Scola B, Campocasso A, N’Dong R, Fournous G, Barrassi L, Flaudrops C, Raoult D: Tentative characterization of new environmental giant viruses by MALDI-TOF mass spectrometry. Intervirology 2010;53:344–353.
  10. Arslan D, Legendre M, Seltzer V, Abergel C, Claverie JM: Distant Mimivirus relative with a larger genome highlights the fundamental features of Megaviridae. Proc Natl Acad Sci USA 2011;108:17486–17491.
  11. Fischer MG, Allen MJ, Wilson WH, Suttle CA: Giant virus with a remarkable complement of genes infects marine zooplankton. Proc Natl Acad Sci USA 2010;107:19508–19513.
  12. Boyer M, Yutin N, Pagnier I, Barrassi L, Fournous G, Espinosa L, Robert C, Azza S, Sun S, Rossmann MG, et al: Giant Marseillevirus highlights the role of amoebae as a melting pot in emergence of chimeric microorganisms. Proc Natl Acad Sci USA 2009;106:21848–21853.
  13. Thomas V, Bertelli C, Collyn F, Casson N, Telenti A, Goesmann A, Croxatto A, Greub G: Lausannevirus, a giant amoebal virus encoding histone doublets. Environ Microbiol 2011;13:1454–1466.
  14. Colson P, Gimenez G, Boyer M, Fournous G, Raoult D: The giant Cafeteria roenbergensis virus that infects a widespread marine phagocytic protist is a new member of the fourth domain of Life. PLoS One 2011;6:e18935.
  15. Iyer LM, Aravind L, Koonin EV: Common origin of four diverse families of large eukaryotic DNA viruses. J Virol 2001;75:11720–11734.
  16. Iyer LM, Balaji S, Koonin EV, Aravind L: Evolutionary genomics of nucleo-cytoplasmic large DNA viruses. Virus Res 2006;117:156–184.
  17. Yutin N, Wolf YI, Raoult D, Koonin EV: Eukaryotic large nucleo-cytoplasmic DNA viruses: clusters of orthologous genes and reconstruction of viral genome evolution. Virol J 2009;6:223.
  18. Koonin EV, Yutin N: Origin and evolution of eukaryotic large nucleo-cytoplasmic DNA viruses. Intervirology 2010;53:284–292.
  19. Lefkowitz EJ, Wang C, Upton C: Poxviruses: past, present and future. Virus Res 2006;117:105–118.
  20. Baroudy BM, Venkatesan S, Moss B: Incompletely base-paired flip-flop terminal loops link the two DNA strands of the vaccinia virus genome into one uninterrupted polynucleotide chain. Cell 1982;28:315–324.
  21. Williams T: The iridoviruses. Adv Virus Res 1996;46:345–412.
  22. Jakob NJ, Müller K, Bahr U, Darai G: Analysis of the first complete DNA sequence of an invertebrate iridovirus: coding strategy of the genome of Chilo iridescent virus. Virology 2001;286:182–196.
  23. Federici BA: Enveloped double-stranded DNA insect virus with novel structure and cytopathology. Proc Natl Acad Sci USA 1983;80:7664–7668.
  24. Federici BA, Vlak JM, Hamm JJ: Comparative study of virion structure, protein composition and genomic DNA of three ascovirus isolates. J Gen Virol 1990;71:1661–1668.
  25. Dixon LK, Abrams CC, Bowick G, Goatley LC, Kay-Jackson PC, Chapman D, Liverani E, Nix R, Silk R, Zhang F: African swine fever virus proteins involved in evading host defence systems. Vet Immunol Immunopathol 2004;100:117–134.
  26. de Villiers EP, Gallardo C, Arias M, da Silva M, Upton C, Martin R, Bishop RP: Phylogenomic analysis of 11 complete African swine fever virus genome sequences. Virology 2010;400:128–136.
  27. Wilson WH, Van Etten JL, Allen MJ: The Phycodnaviridae: the story of how tiny giants rule the world. Curr Top Microbiol Immunol 2009;328:1–42.
  28. Van Etten JL, Lane LC, Dunigan DD: DNA viruses: the really big ones giruses). Annu Rev Microbiol 2010;64:83–99.
  29. Van Etten JL: Unusual life style of giant chlorella viruses. Annu Rev Genet 2003;37:153–195.
  30. Wilson WH, Schroeder DC, Allen MJ, Holden MT, Parkhill J, Barrell BG, Churcher C, Hamlin N, Mungall K, Norbertczak H, et al: Complete genome sequence and lytic phase transcription profile of a Coccolithovirus. Science 2005;309:1090–1092.
  31. Fuhrman JA: Marine viruses and their biogeochemical and ecological effects. Nature 1999;399:541–548.
  32. Raoult D, La Scola B, Birtles R: The discovery and characterization of Mimivirus, the largest known virus and putative pneumonia agent. Clin Infect Dis 2007;45:95–102.
  33. Lwoff A: The concept of virus. J Gen Microbiol 1957;17:239–253.
  34. Boyer M, Madoui M-A, Gimenez G, La Scola B, Raoult D: Phylogenetic and phyletic studies of informational genes in genomes highlight existence of a 4th domain of life including giant viruses. PloS One 2010;5:e15530.
  35. Fischer MG, Suttle CA: A virophage at the origin of large DNA transposons. Science 2011;332:231–234.
  36. Woese CR, Kandler O, Wheelis ML: Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proc Natl Acad Sci USA 1990;87:4576–4579.
  37. Koonin EV, Senkevich TG, Dolja VV: The ancient virus world and evolution of cells. Biol Direct 2006;1:29.
  38. Ivanovski D: Über die Mosaikkrankheit der Tabakspflanze. St Petersb Acad Imp Sci Bull 1892;35:67–70.
  39. Beijerinck MW: Über ein Contagium vivum fluidum als Ursache der Fleckenkrankheit der Tabaksblätter. Verhandelingen der Koninklyke akademie van Wettenschappen te Amsterdam; in Johnson J (ed): Phytopathological Classics No 7. St Paul, American Phytopathological Society, 1942, pp 33–52.
  40. Lustig A, Levine AJ: One hundred years of virology. J Virol 1992;66:4629–4631.
  41. Roening G, Holowczak JA: Evidence for the presence of RNA in the purified virions of vaccinia virus. J Virol 1974;14:704–708.
  42. Filée J, Chandler M: Gene exchange and the origin of giant viruses. Intervirology 2010;53:354–361.
  43. Koonin EV, Wolf YI, Nagasaki K, Dolja VV: The Big Bang of picorna-like virus evolution antedates the radiation of eukaryotic supergroups. Nat Rev Microbiol 2008;6:925–939.
  44. Raoult D: The post-Darwinist rhizome of life. Lancet 2010;375:104–105.
  45. Williams TA, Embley TM, Heinz E: Informational gene phylogenies do not support a fourth domain of life for nucleocytoplasmic large DNA viruses. PLoS One 2011;6:e21080.
  46. Wu D, Wu M, Halpern A, Rusch DB, Yooseph S, Frazier M, Venter JC, Eisen JA: Stalking the fourth domain in metagenomic data: searching for, discovering, and interpreting novel, deep branches in marker gene phylogenetic trees. PLoS One 2011;6:e18011.
  47. Novoa RR, Calderita G, Arranz R, Fontana J, Granzow H, Risco C: Virus factories: associations of cell organelles for viral replication and morphogenesis. Biol Cell 2005;97:147–172.
  48. Suzan-Monti M, La Scola B, Barrassi L, Espinosa L, Raoult D: Ultrastructural characterization of the giant volcano-like virus factory of Acanthamoeba polyphaga Mimivirus. PLoS One 2007;2:e328.
  49. Suzan-Monti M, La Scola B, Raoult D: Genomic and evolutionary aspects of Mimivirus. Virus Res 2006;117:145–155.
  50. Suhre K: Gene and genome duplication in Acanthamoeba polyphaga Mimivirus. J Virol 2005;79:14095–14101.
  51. Filée J: Lateral gene transfer, lineage-specific gene expansion and the evolution of nucleo-cytoplasmic large DNA viruses. J Invertebr Pathol 2009;101:169–171.
  52. Moreira D, Brochier-Armanet C: Giant viruses, giant chimeras: the multiple evolutionary histories of Mimivirus genes. BMC Evol Biol 2008;8:12.
  53. Colson P, Raoult D: Gene repertoire of amoeba-associated giant viruses. Intervirology 2010;53:330–343.
  54. Shackelton LA, Holmes EC: The evolution of large DNA viruses: combining genomic information of viruses and their hosts. Trends Microbiol 2004;12:458–465.
  55. McLysaght A, Baldi PF, Gaut BS: Extensive gene gain associated with adaptive evolution of poxviruses. Proc Natl Acad Sci USA 2003;100:15655–15660.
  56. Evans DH, Stuart D, McFadden G: High levels of genetic recombination among cotransfected plasmid DNAs in poxvirus-infected mammalian cells. J Virol 1988;62:367–375.
  57. Pickup DJ, Ink BS, Parsons BL, Hu W, Joklik WK: Spontaneous deletions and duplications of sequences in the genome of cowpox virus. Proc Natl Acad Sci USA 1984;81:6817–6821.
  58. Raoult D, Boyer M: Amoebae as genitors and reservoirs of giant viruses. Intervirology 2010;53:321–329.
  59. Boyer M, Azza S, Barrassi L, Klose T, Campocasso A, Pagnier I, Fournous G, Borg A, Robert C, Zhang X, et al: Mimivirus shows dramatic genome reduction after intra-amoebal culture. Proc Natl Acad Sci USA 2011;108:10296–10301.
  60. Boyer M, Gimenez G, Suzan-Monti M, Raoult D: Classification and determination of possible origins of ORFans through analysis of nucleocytoplasmic large DNA viruses. Intervirology 2010;53:310–320.
  61. Desnues C, Boyer M, Raoult D: Sputnik, a virophage infecting the viral domain of life. Adv Vir Res 2012;82:63–89.
    External Resources
  62. Yau S, Lauro FM, Demaere MZ, Brown MV, Thomas T, Raftery MJ, Andrews-Pfannkoch C, Lewis M, Hoffman JM, Gibson JA, et al: Virophage control of antarctic algal host-virus dynamics. Proc Natl Acad Sci USA 2011;108:6163–6168.
  63. Edwards RA, Rohwer F: Viral metagenomics. Nat Rev Microbiol 2005;3:504–510.
  64. Angly FE, Willner D, Prieto-Davó A, Edwards RA, Schmieder R, Vega-Thurber R, Antonopoulos DA, Barott K, Cottrell MT, Desnues C, et al: The GAAS metagenomic tool and its estimations of viral and microbial average genome size in four major biomes. PLoS Comput Biol 2009;5:e1000593.
    External Resources
  65. Thurber RV, Haynes M, Breitbart M, Wegley L, Rohwer F: Laboratory procedures to generate viral metagenomes. Nat Protoc 2009;4:470–483.
  66. Ghedin E, Claverie JM: Mimivirus relatives in the Sargasso Sea. Virol J 2005;2:62.
  67. Rusch DB, Halpern AL, Sutton G, Heidelberg KB, Williamson S, Yooseph S, Wu D, Eisen JA, Hoffman JM, Remington K, et al: The Sorcerer II Global Ocean Sampling expedition: northwest Atlantic through eastern tropical Pacific. PLoS Biol 2007;5:e77.
    External Resources
  68. Monier A, Larsen JB, Sandaa RA, Bratbak G, Claverie JM, Ogata H: Marine mimivirus relatives are probably large algal viruses. Virol J 2008;5:12.
  69. Ogata H, Toyoda K, Tomaru Y, Nakayama N, Shirai Y, Claverie JM, Nagasaki K: Remarkable sequence similarity between the dinoflagellate-infecting marine girus and the terrestrial pathogen African swine fever virus. Virol J 2009;6:178.
  70. Loh J, Zhao G, Presti RM, Holtz LR, Finkbeiner SR, Droit L, Villasana Z, Todd C, Pipas JM, Calgua B, et al: Detection of novel sequences related to African swine fever virus in human serum and sewage. J Virol 2009;83:13019–13025.
  71. Kristensen DM, Mushegian AR, Dolja VV, Koonin EV: New dimensions of the virus world discovered through metagenomics. Trends Microbiol 2010;18:11–19.
  72. Condit RC: Principles of virology; in Knipe DM, Howley PM (eds): Fields Virology, ed 5, Philadelphia, Lippincott Williams & Wilkins, 2007.
  73. Moss B: Poxviridae: the viruses and their replication; in Fields BN, Knipe DM, Howley PM (eds): Fields Virology, ed 3. Philadelphia, Lippincott-Raven, 1996, pp 2637–2671.
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