Poxviruses have been prominent in the history of medicine, especially smallpox, caused by Variola virus, which was the target of the first vaccine and which later became the first disease eradicated.

[2][3][4] During the process of assembling the viral capsid, MCPs self-assemble into hexagonal structures, called hexons, containing multiple copies of the MCP.

The ATPases in Varidnaviria are enzymes that package the viral DNA into the capsid during the process of assembling virions.

[4] The subset of the FtsK-HerA superfamily found in Varidnaviria is often called the A32 clade, named after the ATPase-encoding A32(R) gene of Vaccinia virus.

[11] The vertical SJR-MCPs of Halopanivirales, assigned to the kingdom Helvetiavirae, unlike SJR folds found outside of Varidnaviria, show a relation to a group of proteins that includes the Cupin superfamily and nucleoplasmins, pointing to a possible origin of the major capsid protein of Varidnaviria among this group.

[13] A molecular phylogenetic analysis suggests that Helvetiavirae had no involvement in the origin of the Bamfordvirae DJR-MCP and that they probably derive from the class Tectiliviricetes.

[5][8][15] The initial bacterial symbiont is likely to have become mitochondria, with mitochondrial linear plasmids descended from tectiviruses remaining.

[4] Another divergent lineage reached the nucleus and recombined with transposons, becoming polintons, which may have been the first eukaryotic viruses in Bamfordvirae or related to the first ones.

This viewpoint is based on Autolykiviruses having broad host ranges, infecting and killing many different strains of various bacteria species, in contrast to tailed bacteriophages, which have more limited host ranges, as well as on the apparently large number of marine non-tailed dsDNA viruses.

[24] Poxviruses infect many animals and typically cause non-specific symptoms paired with a characteristic rash that is called a pox.

[25] ASFV is usually asymptomatic in its natural reservoirs but causes a lethal hemorrhagic fever in domestic pigs that is a concern for agricultural production.

[26] Many viruses in Varidnaviria encode the enzyme integrase, allowing them to integrate their genome into their host and behave like transposons.

This integration of viral DNA into the host's genome is a form of horizontal gene transfer between unrelated organisms, although polintons are typically transmitted vertically from parent to child.

[25] Human adenoviruses were the first DJR-MCP viruses in Varidnaviria to have their MCPs analyzed, standing out for having jelly roll folds that were perpendicular, rather than parallel, to the capsid surface.

[2] The establishment of Varidnaviria has allowed for newly discovered and related, yet divergent, viruses to be classified in higher taxa.

This includes proposed families such as Finnlakeviridae, which would be the only family in the realm with a single-stranded DNA genome, Autolykiviridae, which have a broad host range and which may play a major role in the deaths of marine bacteria, and the "Odin" group, which encode a protein that has no known relation to any other proteins in place of the FtsK-HerA superfamily ATPase.