Adintoviruses: a proposed animal-tropic family of midsize eukaryotic linear dsDNA (MELD) viruses

Abstract

Polintons (also known as Mavericks) were initially identified as a widespread class of eukaryotic transposons named for their hallmark type B DNA polymerase and retrovirus-like integrase genes. It has since been recognized that many polintons encode possible capsid proteins and viral genome-packaging ATPases similar to those of a diverse range of double-stranded DNA viruses. This supports the inference that at least some polintons are actually viruses capable of cell-to-cell spread. At present, there are no polinton-associated capsid protein genes annotated in public sequence databases. To rectify this deficiency, we used a data-mining approach to investigate the distribution and gene content of polinton-like elements and related DNA viruses in animal genomic and metagenomic sequence datasets. The results define a discrete family-like clade of viruses with two genus-level divisions. We propose the family name Adintoviridae, connoting similarities to adenovirus virion proteins and the presence of a retrovirus-like integrase gene. Although adintovirus-class PolB sequences were detected in datasets for fungi and various unicellular eukaryotes, sequences resembling adintovirus virion proteins and accessory genes appear to be restricted to animals. Degraded adintovirus sequences are endogenized into the germlines of a wide range of animals, including humans.

Keywords: Maverick; adenain; capsid; polB; polinton; recombination; transposon.

Figure 1.

PolB BLASTP relationships. PolB protein sequences were subjected to all-against-all sequence similarity network analysis with a BLASTP E-value cut-off of 1e-06. Supplementary File S1 presents an interactive version of Fig. 1 that can be viewed using Cytoscape software (https://cytoscape.org). Supplementary File S2 contains sequence compilations for PolB and other proteins.

Figure 2.

Genome maps of two representative adintoviruses. See main text for descriptions of gene names. Black bars denote inferred termini. Supplementary Table S1 presents accession numbers and full Linnaean designations of animal hosts.

Figure 3.

Phylogenetic trees comprised of WGS hits for Alpha or Beta adintovirus PolB sequences (left and right panels, respectively). Hits from insect datasets are colored yellow, hits from tetrapod datasets are red, and fungus-associated hits are blue. All other types of eukaryotes are represented by black lines. Annotated branches show two Alpha adintovirus sequences associated with bovine (Bos) lung samples clustering with adintovirus sequences from insect datasets, suggesting an environmental insect source. In contrast, exemplar Mayetiola and Terrapene adintoviruses cluster with sequences found in other insect or terrestrial vertebrate datasets, respectively. Similarly, adintovirus PolB-like sequences from Powellomyces and Rhizophagus fungi cluster with sequences from other types of fungi. Supplementary Files S3 and S4 are Nexus-format versions of the figure that can be viewed interactively using FigTree software (http://tree.bio.ed.ac.uk/software/figtree/).

Figure 4.

An endogenized Beta adintovirus relic found on human chromosome 7. Degraded pseudogenes interrupted by nonsense and frameshift mutations were reconstructed based on alignments to the protein sequences of Terrapene box turtle adintovirus. Question marks indicate that the reconstructed gene does not yield hits in BLAST searches of GenBank’s viruses taxon. Tentative gene assignments are based on synteny with the Terrapene adintovirus. The reconstructed Hexon, GasderminX, and PolB protein sequences yield DELTA-BLAST hits with E-values of 1e-21, 4e-05, and 3e-25, respectively. Supplementary File S5 presents an annotated GenBank-format nucleotide map of the human chromosome 7 endogenized adintovirus.

Figure 5.

MELD viruses (and related elements) with adintovirus-like PolB genes. Greek letters indicate genes similar to Alpha or Beta adintoviruses in BLASTP or DELTA-BLAST searches. “Ad-” indicates similarity to adenovirus sequences. Fiber, predicted structural or primary sequence similarity to bacteriophage tail fibers or coiled-coil proteins; Lectin, predicted structural similarity to galactose-binding domains; SET, sequence similarity to the S-adenosyl methionine-binding pocket of cellular histone-lysine methyltransferases; TRAF, predicted structural similarity to TNF receptor-associated factor 3; UCH, predicted structural similarity to ubiquitin C-terminal hydrolases; IVa2, sequence similarity to adenovirus IVa2 viral genome-packaging ATPases; Dcm, predicted structural similarity to cytosine DNA methyltransferases; TBP, similar to TATA binding proteins; Matrix/Capsid/NC/Pro, similarities to retroviral Gag and retropepsin; S3H, poxvirus D5-like superfamily 3 helicase.

Figure 6.

MELD viruses with other replicases. Greek letters indicate genes with sequences similar to Alpha or Beta adintoviruses in BLASTP searches. Sequences similar to adenoviruses are marked with “Ad-.” Yellow flags represent predicted tRNA genes. dUTPase, similar to poxvirus deoxy-UTP diphosphatases; Fiber, similarity to bacteriophage tail fibers or other coiled-coil proteins; Tapemeasure, similarity to phage tail tape measure proteins; S1H, RecD/Pif1-like superfamily 1 helicase; YRec, homolog of phage tyrosine recombinases; DnaA-like, sequence distantly similar to DnaA and DnaB-like helicases; VI, similar to adenovirus virion core protein six; PolA, DNA polymerase family A (Pfam : 00476); S3H superfamily 3 helicase similar to those observed in virophages and megaviruses; S2H, superfamily 2 helicase similar to DEAD-box helicase of Yellowstone Lake virophage 7 (YP_009177696); SLATT, homolog of host SMODS and SLOG-associating 2TM effector domain proteins; VLTF, homolog of mimivirus VLTF3-like transcription factor. See main text for information about other gene names.

Figure 7.

Genome maps for non-animal parvoviruses, bidnaviruses, and proposed bidnaparvoviruses. GIIM, similarity to group II intron maturases; tailspike, similarity to bacteriophage short tail fibers.