Duplodnaviria

Duplodnaviria is a realm of viruses that includes all double-stranded DNA viruses that encode the HK97 fold major capsid protein. The HK97 fold major capsid protein (HK97 MCP) is the primary component of the viral capsid, which stores the viral deoxyribonucleic acid (DNA). Viruses in the realm also share a number of other characteristics, such as an icosahedral capsid, an opening in the capsid called a portal, a protease enzyme that empties the inside of the capsid prior to DNA packaging, and a terminase enzyme that packages viral DNA into the capsid. There are three groups of viruses in the realm: caudoviruses, herpesviruses, and the putative group mirusviruses.

Caudoviruses are one of the most abundant group of viruses on Earth and are ubiquitous worldwide. They infect prokaryotes and are a major cause of death in them, which contributes to the recycling of organic material in a process called viral shunt. Caudoviruses have been used as model organisms to study biological processes and as a form of therapy to treat bacterial infections. Herpesviruses infect animals and are commonly associated with diseases such as herpes and chickenpox. Mirusviruses infect microscopic eukaryotes and are among the most common eukaryotic viruses in sunlit oceans. Many duplodnavirians are able to enter a latent state in which they persist in cells without forming virions. This is called the lysogenic cycle and contrasts with the lytic cycle, which produces virions.

Duplodnaviria likely predates the last universal common ancestor (LUCA) of cellular life and was present in the LUCA. Caudoviruses in particular were likely already diverse by the time the LUCA emerged. Mirusviruses are related to viruses in the phylum Nucleocytoviricota in the realm Varidnaviria because they encode the core replication- and transcription-related proteins found in nucleocytoviruses. It is unclear, however, which realm these genes originate from. In any case, herpesviruses appear to have lost most of these genes through reductive evolution. Outside of the realm, an HK97-like fold is only found in encapsulins, which form nanocompartments in prokaryotes and are likely derived from duplodnaviruses.

Duplodnaviria contains one kingdom, which is divided into two phyla that contain two lineages of viruses in the realm: caudoviruses and herpesviruses. This taxonomy can be visualized as follows:

The realm also contains mirusviruses, which have not been assigned to any taxon officially but which constitute the putative phylum Mirusviricota. As all viruses in the realm are double-stranded DNA (dsDNA) viruses, the realm belongs to Group I: dsDNA viruses of Baltimore classification, a classification system based on a virus's manner of messenger RNA (mRNA) production that is often used alongside standard virus taxonomy, which is based on evolutionary history. Realms are the highest level of taxonomy used for viruses and Duplodnaviria is one of seven. The others are Adnaviria, Monodnaviria, Riboviria, Ribozyviria, Singelaviria, and Varidnaviria.

All viruses in Duplodnaviria contain an icosahedral capsid that is composed of a major capsid protein (MCP) that contains a unique folded structure, called the HK97 fold, named after the folded structure of the MCP of the bacterial virus HK97. The conserved elements of the HK97 fold, found in all duplodnavirians, are the axial (A) domain, the peripheral (P) domain, the extended (E) loop, and the N-terminal (N) arm. Many MCPs contain additional elements, such as the insertion (I) domain, which is grafted onto the A-domain, and the glycine-rich (G) loop, found in bacteriophage HK97's MCP. Other hallmark traits among viruses in the realm involve the structure and assembly of capsids and include a portal protein that forms the opening of the capsid, a protease that empties the capsid before viral DNA is packaged, and a terminase enzyme that packages viral DNA into the capsid. In herpesviruses, their proteases are often referred to as assemblins.

After HK97 MCPs have been synthesized by the host cell's ribosomes, the viral capsid is assembled from them with the proteins bonding to each other. The first product of capsid assembly is a procapsid, also called prohead for caudoviruses. Procapsids are roughly spherical, lumpy, and thick. Assembly of procapsids is driven by scaffold proteins that guide the geometric construction of the procapsid. In the absence of such proteins, the delta domain of the MCP, which faces toward the inside of the capsid, acts as a scaffold protein. A cylindrical opening the capsid, the portal, that serves as the entrance and exit for viral DNA is created with portal proteins at one of the 12 vertices of the capsid. After capsid assembly, scaffold proteins are removed from the inside of the capsid by the capsid maturation protease, which may be part of the scaffolding. Scaffold proteins may be removed intact or after the protease breaks them down in a process called proteolysis, either of which leaves the inside of the procapsid empty.

At the same time as capsid assembly, replication of viral DNA occurs, and long molecules of DNA containing numerous copies of the viral genome, called concatemers, are created. The enzyme terminase, made of two subunits (large and small), finds the viral DNA inside of the cell via the small subunit, cuts the concatemers, and creates the endings (termini) of the genomes. Terminase recognizes a packaging signal in the genome and cuts the nucleic acid, creating a free end that it binds to. The terminase, now bound to the concatemer, attaches itself to the capsid portal and begins translocating the DNA from outside the capsid to the inside, using energy generated from ATP hydrolysis by its large subunit. As more DNA is inserted into the capsid, the capsid expands in size, becomes thinner, and its surface becomes flatter and more angular. Once the genome is completely inside, terminase cuts the concatemer again, completing packaging. Terminase then detaches itself from the portal and proceeds to repeat this process until all genomes in the concatemer have been packaged into capsids.