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. 2024 Jul 17;15(7):e0103524.
doi: 10.1128/mbio.01035-24. Epub 2024 Jun 4.

Mriyaviruses: small relatives of giant viruses

Natalya Yutin  1 , Pascal Mutz  1 , Mart Krupovic  2 , Eugene V Koonin  1
Affiliations

Mriyaviruses: small relatives of giant viruses

Natalya Yutin et al. mBio. .

Abstract

The phylum Nucleocytoviricota consists of large and giant viruses that range in genome size from about 100 kilobases (kb) to more than 2.5 megabases. Here, using metagenome mining followed by extensive phylogenomic analysis and protein structure comparison, we delineate a distinct group of viruses with double-stranded (ds) DNA genomes in the range of 35-45 kb that appear to be related to the Nucleocytoviricota. In phylogenetic trees of the conserved double jelly-roll major capsid proteins (MCPs) and DNA packaging ATPases, these viruses do not show affinity to any particular branch of the Nucleocytoviricota and accordingly would comprise a class which we propose to name "Mriyaviricetes" (after Ukrainian "mriya," dream). Structural comparison of the MCP suggests that, among the extant virus lineages, mriyaviruses are the closest one to the ancestor of the Nucleocytoviricota. In the phylogenetic trees, mriyaviruses split into two well-separated branches, the family Yaraviridae and proposed new family "Gamadviridae." The previously characterized members of these families, yaravirus and Pleurochrysis sp. endemic viruses, infect amoeba and haptophytes, respectively. The genomes of the rest of the mriyaviruses were assembled from metagenomes from diverse environments, suggesting that mriyaviruses infect various unicellular eukaryotes. Mriyaviruses lack DNA polymerase, which is encoded by all other members of the Nucleocytoviricota, and RNA polymerase subunits encoded by all cytoplasmic viruses among the Nucleocytoviricota, suggesting that they replicate in the host cell nuclei. All mriyaviruses encode a HUH superfamily endonuclease that is likely to be essential for the initiation of virus DNA replication via the rolling circle mechanism.

Importance: The origin of giant viruses of eukaryotes that belong to the phylum Nucleocytoviricota is not thoroughly understood and remains a matter of major interest and debate. Here, we combine metagenome database searches with extensive protein sequence and structure analysis to describe a distinct group of viruses with comparatively small genomes of 35-45 kilobases that appear to comprise a distinct class within the phylum Nucleocytoviricota that we provisionally named "Mriyaviricetes." Mriyaviruses appear to be the closest identified relatives of the ancestors of the Nucleocytoviricota. Analysis of proteins encoded in mriyavirus genomes suggests that they replicate their genome via the rolling circle mechanism that is unusual among viruses with double-stranded DNA genomes and so far not described for members of Nucleocytoviricota.

Keywords: AlphaFold; HUH superfamily endonucleases; Mriyaviricetes; Nucleocytoviricota; double jelly-roll fold; rolling circle replication; virus evolution.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig 1
Fig 1
Phylogenetic trees of proteins conserved in mriyaviruses and the rest of the members of Nucleocytoviricota. (A) Major capsid protein (MCP); (B) DNA packaging ATPase; and (C) virus late transcription factor 3 (VLTF3). The IQTree bootstrap values are indicated for the key branches. The trees in newick format are accessible at https://ftp.ncbi.nih.gov/pub/yutinn/mriya_2024.
Fig 2
Fig 2
Genome maps of selected mriyaviruses. Genes with predicted functions are shown by color-coded block arrows. Circles near contig names indicate contigs with direct terminal repeats. Abbreviations: ATPase, DNA packaging ATPase; HUH, mriyavirus HUH endonuclease; HUH_long, conserved gamadvirus protein containing a C-terminal domain homologous to mriyavirus HUH endonuclease; ITR, inverted terminal repeats; MCP, major capsid protein; mCP, minor capsid protein; PDDEXK, PDDEXK superfamily endonuclease; PolB, family B DNA polymerase; RuvC, RuvC-like Holliday junction resolvase homologous to poxvirus A22 resolvase; ssb, single-strand DNA binding protein; VLTF2, virus late transcription factor 2; VLTF3, virus late transcription factor 3; Mriya_1, conserved domain homologous to yaravirus gene 1; Mriya_48, yaravirus gene 48 homolog; Mriya_50, yaravirus gene 50 homolog; Mriya_51, yaravirus gene 51 homolog. Genome maps of all 60 mriyavirus representative genomes are available at https://ftp.ncbi.nih.gov/pub/yutinn/mriya_2024.
Fig 3
Fig 3
Patterns of protein presence-absence in mriyaviruses. The MCP tree was rooted between Yaraviridae and “Gamadviridae” for visualization. Circles at branches indicate contigs with direct terminal repeats. Genomes retrieved from GenBank are denoted with blue font. The middle panel shows genome length. Conserved proteins are abbreviated as in Fig. 2. The coloring in the helicase column indicates: turquoise, group 1 SF3 family helicase (SF3_hel1 group); pink, group 2 SF3 family helicase (SF3_hel2); and orange, SF2 family helicase (SF2_hel).
Fig 4
Fig 4
Comparison of the predicted structures of mriyavirus major capsid proteins (MCPs) with structures of MCPs of other members of the kingdom Bamfordvirae. The heat map reflects the z-scores obtained in structural comparisons of the MCPs using Dali (color gradient shown to the right of the heat map). The dendrogram shows clustering of the MCPs by the z-scores. The abbreviations are as follows: ACMV, Acanthamoeba castellanii medusavirus (BBI30317); ALV, Vibrio phage 1.020.O._10N.222.48.A2 (AUR82054); APMV, Acanthamoeba polyphaga mimivirus (ADO18196.2); ASFV, African swine fever virus (PDB id: 6ku9); BpV1, Bathycoccus sp. RCC1105 virus BpV1 (YP_004061587); CeV-01B, Chrysochromulina ericina virus 01B (YP_009173446); EhV-86, Emiliania huxleyi virus 86 (YP_293839); Fausto, faustovirus (PDB id: 5j7o); Gamad_1, Ga0181388_1000587_17; Gamad_2, Ga0314846_0002864_7; Gamad_4, pleuro_group_Assembly_Contig_24_24; IIV3, invertebrate iridescent virus 3 (YP_654586); MV, Marseillevirus marseillevirus (YP_003407071); OtV5, Ostreococcus tauri virus 5 (YP_001648266); P1-CB, Polinton 1 of Caenorhabditis briggsae; P1-DY, Polinton 1 of Drosophila yakuba; PBCV-1, Paramecium bursaria chlorella virus 1 (PDB id: 5tip); PEV2, Pleurochrysis sp. endemic virus 2 (AUD57312); PLVs, polinton-like viruses; PM2, Pseudoalteromonas phage PM2 (PDB id: 2vvf); PRD1, Enterobacteria phage PRD1 (PDB id:1hx6); RanaV, Ranavirus maximus (YP_009272725); SkuldV1, Lokiarchaea virus SkuldV1 (UPO70972); STIV, Sulfolobus turreted icosahedral virus 1 (PDB id: 3j31); TsV, Tetraselmis virus 1 (YP_010783039); VvCV, Vermamoeba vermiformis clandestinovirus (QYA18424); Yara_1, Ga0364485_12008_8; Yara_2, Ga0466970_0005716_5; Yara_3, Yara_group_Contig_26_5; YaV, Yaravirus brasiliensis (QKE44414).
Fig 5
Fig 5
The helicase-containing proteins of mriyaviruses. (A) Domain architectures of the helicase-containing proteins of mriyaviruses and the poxvirus primase-helicase (D5) shown for comparison. The asterisk indicates that in the SF3_Hel1 group, most of the AEP homologs contain disrupted catalytic motifs and thus appear to be inactivated. DUF, domain of unknown function; MPOX, monkeypox virus. (B) Sequence segments of AEP catalytic motifs of selected SF2_Hel and SF3_Hel1 proteins. The residues implicated in catalysis are shown with white letters on red background. (C) Structural models of predicted AEPs of the SF3_Hel1 and SF2_Hel groups of mriyavirus proteins compared to the structure of the AEP domain of MPOX (pdb accession indicated). M1–M4 denote AEP catalytic motifs shown in panel B. (D) Structural model of the DUF located at the N-terminus of the SF3_Hel2 proteins.
Fig 6
Fig 6
Sequence and structure conservation in the HUH endonucleases of mriyaviruses. (A) Alignment of the sequence segments of the HUH superfamily endonucleases containing the characteristic motifs I–III. The N-terminal motif I consists of hydrophobic residues, motif II consists of HUH (H: Histidine, U: hydrophobic residue), and C-terminal motif III (Yx2-3K; Y: tyrosine, x: any residue, K: lysine, blue). (B) A representative predicted structure of a mriyavirus HUH endonuclease superposed with the crystal structure of protein ORF119 from Sulfolobus islandicus rod-shaped virus 1 (green, pdb 2X3G-A, z-score 7.7). Yaravirus HUH endonuclease (MT293574_27) colored by plddt score. (C) Configuration of the catalytic amino acid residues of motifs II and III in the predicted structure of the mriyavirus HUH endonuclease (yaravirus MT293574_27, colored by plddt score). (D) Superposition of the structural models of the two HUH endonuclease domains of gamadviruses (short: KY346835_11 [green, aa 31–224, aa 1–30 unstructured, clipped off for representation], long: KY346835_10 [orange, aa 1353–1574 with additional inserted loop shown in purple, aa 104–1450])].
Fig 7
Fig 7
Comparison of the structural models of Mriya_48 protein and iridovirus envelope protein. (A) Iridovirus enveloped protein (ORF056L; NP_612278); (B) Ple2_KY346835_19; (C) Ga0206648_1000510_21; (D) Superposition of ORF056L (green) and Ple2_KY346835_19 (purple); (E) Superposition of ORF056L (green) and Ga0206648_1000510_21 (cyan). In panels A–C, the structures are colored according to the plddt score.
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References

    1. Abergel C, Legendre M, Claverie JM. 2015. The rapidly expanding universe of giant viruses: Mimivirus, Pandoravirus, Pithovirus and Mollivirus. FEMS Microbiol Rev 39:779–796. doi:10.1093/femsre/fuv037 - DOI - PubMed
    1. Koonin EV, Yutin N. 2019. Evolution of the large nucleocytoplasmic DNA viruses of eukaryotes and convergent origins of viral gigantism. Adv Virus Res 103:167–202. doi:10.1016/bs.aivir.2018.09.002 - DOI - PubMed
    1. Raoult D, Audic S, Robert C, Abergel C, Renesto P, Ogata H, La Scola B, Suzan M, Claverie J-M. 2004. The 1.2-megabase genome sequence of mimivirus. Science 306:1344–1350. doi:10.1126/science.1101485 - DOI - PubMed
    1. Claverie J-M, Grzela R, Lartigue A, Bernadac A, Nitsche S, Vacelet J, Ogata H, Abergel C. 2009. Mimivirus and Mimiviridae: giant viruses with an increasing number of potential hosts, including corals and sponges. J Invertebr Pathol 101:172–180. doi:10.1016/j.jip.2009.03.011 - DOI - PubMed
    1. Nasir A, Kim KM, Caetano-Anolles G. 2012. Giant viruses coexisted with the cellular ancestors and represent a distinct supergroup along with superkingdoms Archaea, Bacteria and Eukarya. BMC Evol Biol 12:156. doi:10.1186/1471-2148-12-156 - DOI - PMC - PubMed

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