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. ==Distribution==