Replication of Viral RNA

The replication of RNA is a phenomenon unique to viruses Transcription of RNA from an RNA template requires an RNA-dependent RNA polymerase, a virus-coded enzyme not found in uninfected celts. The replication of viral RNA requires first the synthesis of complementary RNA, which then serves as a template for making more viral RNA.

Where the viral RNA is of minus sense (orthomyxoviruses, paramyxoviruses, rhabdoviruses, filoviruses, arenaviruses, and bunya vi ruses), the complementary RNA will be of plus sense. Whereas most transcripts from such minus sense viral RNA are subgenomic mRNA molecules, some full-length plus strands are also made, in order to serve as templates for viral RNA synthesis (replication). For some viruses there is evidence that the RNA polymerases used for transcription and replication are distinct

In the case of the plus sense RNA viruses (picornaviruses, caliciviruses, togaviruses, flaviviruses, and coronaviruses) the complementary RNA is minus sense. Several viral RNA molecules can be transcribed simultaneously from a single complementary RNA template, each RNA transcript being the product of a separately bound polymerase molecule. The resulting structure, known as the rephcalive intermediate, is therefore partially double-stranded, with single-stranded tails. Initiation of replication of Picornavirus and cal-icivirus RNA, like that of adenovirus DNA, requires a protein, rather than an oligonucleotide, as primer. This small protein is covalently attached to the 5r terminus of nascent plus and minus RNA strands, as well as to viral RNA, but not to mRNA. Little is known about what determines whether a given Picornavirus plus sense RNA molecule will be directed (1) to a "replication complex/' bound to smooth endoplasmic reticulum, where it serves as a template for transcription by RNA-dependent RNA polymerase into minus sense RNA; or (2) to a ribosome, where it serves as mRNA for translation into protein; or (3) to a procapsid, with which it associates to form a virion.

Retroviruses have a genome consisting of plus sense ssRNA. Unlike other RNA viruses, retroviruses replicate via a DNA intermediate. The virion-associated reverse transcriptase, using a transfer RNA (tRNA) molecule as a primer, makes a ssDNA copy Then, functioning as a ribonuclease, the same enzyme removes the parental RNA molecule from the DNA-RNA hybrid. The free minus sense ssDNA strand is then copied to form a linear dsDNA molecule, which contains an extra copy of sequences necessary for integration and expression, known as the tang terminal tepeat (UR), at each end This dsDNA then circularizes and integrates into cellular DNA. Transcription of viral RNA occurs from this integrated (proviral) DNA.

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