Ribozyviria is a realm of animal viruses. Viruses in the realm are characterized by the presence of ribozymes in the genome that are involved in replication. They encode one protein, DAg, which associates with the single-stranded, negative-sense RNA genome, forming a rod-shaped ribonucleoprotein (RNP) complex. The RNP complex is surrounded by an envelope that is acquired from a helper virus. The most well studied ribozyvirian is the hepatitis D virus (HDV), and its helper virus is the hepatitis B virus. Because of the dependency on helper viruses, ribozyvirians infect the same cells as their helper viruses. Ribozyvirians infect cells by attaching to the surface with helper virus-derived spike proteins on the surface of the envelope. The envelope fuses with the cell membrane, releasing the RNP into the cell, where it moves to the nucleus for replication. A host RNA polymerase replicates the genome in a double rolling circle process, during which individual progeny genomes are excised from concatemers by viral ribozymes. The DAg protein is translated from messenger RNA and binds to the genome. Envelopes are then obtained before progeny viruses leave the cell. Ribozyvirians infect a variety of animals, including amphibians, birds, fish, insects, mammals, and reptiles. In humans, HDV causes the liver disease hepatitis D, with symptoms such as hepatitis, cirrhosis, and liver cancer. The origin of ribozyvirians is unclear, but they have been proposed to originate from an escaped gene from a cellular host or mis-spliced RNA. HDV was the first virus of the realm to be discovered, in 1977, and was the only known ribozyvirian for about 40 years. Starting in the late 2010s, other members began to be discovered, and in 2021, both the realm Ribozyviria and its sole family, Kolmioviridae, were established.
Classification Ribozyviria contains one family, Kolmioviridae, with no intermediate taxa between the ranks of realm and family. Kolmioviridae contains 11 genera. This is shown hereafter:
Realm: Ribozyviria Family: Kolmioviridae Genus: Daazvirus Genus: Dagazvirus Genus: Daletvirus Genus: Dalvirus Genus: Deevirus Genus: Deltavirus, also called the hepatitis D virus Genus: Dobrovirus Genus: Donvirus Genus: Perideltavirus Genus: Perithurisazvirus Genus: Thurisazvirus
Characteristics
Genome and proteins Ribozyvirians have negative-sense single-stranded RNA (–ssRNA) genomes that are about 1.5–1.7 kilobases in length. The genome is a non-segmented, covalently-closed circular RNA (cccRNA) molecule that organizes into a rod-like shape due to a high amount of self-complementarity. Their genomes contain at least two ribozymes: one on the genomic (negative-sense) strand, and one on the antigenomic (positive-sense) strand. The only protein encoded by ribozyvirians is the delta antigen (DAg), encoded in the antigenome. Some deltaviruses express two forms of DAg, called small delta antigen (S-DAg) and large delta antigen (L-DAg). L-DAg is almost identical to S-DAg; the only difference is that L-DAg contains 19 or 20 additional amino acid residues, created by genome editing by the host.
Structure
The structure of ribozyvirians has only be detailed for deltaviruses. The extracellular particles (virions) of deltaviruses are roughly spherical, pleomorphic in shape and about 36–43 nanometers (nm) in diameter. Virions consist of a rod-shaped genomic ribonucleoprotein (RNP) complex surrounded by a viral envelope with spikes derived from a helper virus. The RNP complex consists of the genome and the nucleoprotein DAg, which associates with the genome. The quantity of S-DAg and L-DAg bound to the genome is variable, but there is about a 70 to 1 protein:RNA ratio.
Life cycle The replication process of ribozyvirians is only known for deltaviruses. They enter host cells by attaching to receptors on the cell surface with their envelope proteins, which are derived from helper viruses. Because of this dependency on helper viruses, ribozyvirians infect the same cells as their helper viruses. After attachment, the envelope fuses with the host cell membrane, releasing the RNP complex into the cell. There, the RNP moves to the cell nucleus, where the genome is replicated. The genome is replicated during a double rolling circle process by a host DNA-directed RNA polymerase II enzyme. During replication, ribozymes in the genome and antigenome cleave concatemers of progeny genomes and ligate individual progeny genomes into a circular form. Replication begins with the RNA polymerase replicating the genome in a loop around the genome, producing a continuous, linear strand of numerous copies (a concatemer) of the antigenome. Ribozymes in the antigenome self-cleave the concatemer to produce individual linear antigenomes. These strands ligate to produce circular antigenomic molecules. The circular antigenome is then replicated in the same manner as the genome, creating a concatemer of genomic strands. Ribozymes in the genome self-cleave this concatemer to produce individual linear genomes, which are ligated into circular genomic molecules. Messenger RNA (mRNA) encoding DAg is transcribed from the negative-sense genome. Expression of DAg induces packaging of RNPs into envelopes made from the Golgi apparatus. These envelopes contain proteins of the helper virus and facilitate budding from the surface of the cell. For deltaviruses, the envelope of hepatitis B virus (HBV) is recruited through farnesylation, which is a post-translational attachment of a hydrophobic molecule to a cysteine residue at the end (C-terminus) of L-DAg's amino acid sequence. This facilitates an interaction between the RNP and the HBV envelope to recruit the envelope. Only genomic RNA molecules that fold into a rod-shape and have DAgs bound to them are packaged into virions. Antigenomes (i.e. positive-sense strands) are not found in virions.
Dependency on helper viruses Ribozyvirians are believed to be dependent on evolutionarily unrelated helper viruses to complete their life cycle. Identified helper viruses include hepatitis B virus for deltaviruses and arenaviruses for daletviruses. Other potential helper viruses include herpesviruses, flaviviruses, retroviruses, and poxviruses.
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