RNA genome

Very few self-sufficient viruses have only 60 protein chains in their shells. The satellite viruses do not themselves encode all of the functions required for their replication and are therefore not self-sufficient. The first satellite virus to be discovered, satellite tobacco necrosis virus, which is also one of the smallest known with a diameter of 180 A, has a protein shell of 60 subunits. This virus cannot replicate on its own inside a tobacco cell but needs a helper virus, tobacco necrosis virus, to supply the functions it does not encode. The RNA genome of the satellite virus has only 1120 nucleotides, which code for the viral coat protein of 195 amino acids but no other protein. With this minimal genome the satellite viruses are obligate parasites of the viruses that parasitize cells. 

The human immunodeficiency vims (HIV) is the causative agent of the acquired immunodeficiency syndrome (AIDS). HIV is a retrovirus, whose replication includes the transcription of the single-stranded RNA genome into double stranded DNA (reverse transcription) and the covalent insertion of the DNA... 

The infectious cycle of a (+)-strand RNA virus such as the hepatitis C virus differs by the fate of the viral RNA genome in the infected cell. Upon entry into the cell, the HCV genome is used as a messenger RNA to drive the synthesis of a large polyprotein precursor of about 3,000 residues [2]. The structural proteins are excised from the precursor by host cell signal peptidase. 

Westerhout EM, Ooms M, Vink M, Das AT, Berkhout B (2005) HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome. Nucleic Acids Res 33 796-804... 

Lee R., Kaushik N., Modak M.J., Vi-NAYAK R., Pandey V. N. Polyamide nucleic acid targeted to the primer binding site of the HlV-1 RNA genome blocks in vitro HlV-1 reverse transcription. Biochemistry 1998 37 900-910. 

A number of bacterial viruses have RNA genomes. The best-known bacterial RNA viruses have single-stranded RNA. Interestingly, the bacterial RNA viruses known in the enteric bacteria group infect only bacterial cells which behave as gene donors (males) in genetic recombination. This restriction to male bacterial cells arises because these viruses infect bacteria by attaching to male-specific pili. Since such pili are absent on female cells, these RNA viruses are unable to attach to the females, and hence do not initiate infection in females. 

The majority of viruses that infect plants have single-stranded, positive-sense RNA genomes. It has therefore been necessary to use infectious cDNA clones for the in vitro manipulation of RNA viruses, allowing them to be developed as effective tools for the commercial production of target proteins in plants. This approach has also been used to study the genetic and metabolic profiles of both viruses and their host plants. Siegel [14] conceptualized the potential use of RNA viruses as expression vectors. Brome mosaic virus (BMV) and Tobacco mosaic vims (TMV) were the first two RNA viruses to be converted into expression vectors. These vectors have since been pro-... 

An additional virus that has more recently gained some attention as a possible vector is that of the sindbis virus. A member of the alphavirus family, this ssRNA virus can infect a broad range of both insect and vertebrate cells. The mature virion particles consist of the RNA genome com-plexed with a capsid protein C. This, in turn, is enveloped by a lipid bilayer in which two additional viral proteins (El and E2) are embedded. The E2 polypeptide appears to mediate viral binding to the surface receptors of susceptible cells. The major mammalian cell surface receptor it targets appears to be the highly conserved, widely distributed laminin receptor. 

Reverse transcriptase is an RNA-dependent DNA polymerase that requires an RNA template to direct the synthesis of new DNA. Retroviruses, most notably HIV, use this enzyme to repHcate their RNA genomes. DNA synthesis by reverse transcriptase in retroviruses can be inhibited by AZT. ddC, and ddl. 

The hepatitis delta virus (HDV) ribozyme is part of the circular single stranded RNA genome of the hepatitis delta virus which consists of a total of 1700 nucleotides. The HDV ribozyme is required for the processing of multimers of the genomic linear RNA transcripts to unit length by catalyzing a transesterification reaction that results in self cleavage [23]. 

The next stage is to ensure that the recombinant DNA molecule is copied by the enzymes which s)mthesize nucleic acids. These DNA and RNA polymerases synthesize an exact copy of either DNA or RNA from a pre-existing molecule. In this way the DNA polymerase duplicates the chromosome before each cell division such that each daughter cell will have a complete set of genetic instructions which are then passed to the newly formed RNA by RNA polymerase. While both DNA and RNA polymerase require a preformed DNA template, some viruses (such as HIV) have an RNA genome. To duplicate that genome, and incorporate it into a bacterial or mammalian cell, the viruses encode a reverse transcriptase enzyme which produces a DNA copy from an RNA template. 

Initiation of reverse transcription in HIV-infected cells relies on a critical RNA-RNA interaction between tRNA y s, which is preferentially packaged into the viral particle, and a specific viral RNA seqnence. The 3 -terminaI 18 nucleotides of tRNA y are complementary to the primer binding site (PBS) sequence located in the 5 -Iong terminal repeat (LTR) of the viral RNA genome (Figure 10.3). The UUU anticodon of the tRNA is complementary to and binds to an adenosine rich loop located 8 nucleotides upstream (5 ) of the PBS. This RNA-RNA duplex which is formed when tRNA y s binds to the PBS fits within the active site of HIV-1 reverse transcriptase, bnt mnitiple interactions between the viral RNA and tRNA y are necessary for efficient initiation of reverse transcription. This interaction nucleates the reverse transcription complex which contains viral RNA, reverse transcriptase, tRNA y pl , nncleocapsid p7, and Vpr (Viral protein R), as well as multiple host factors." ... 

Many viruses and retroviruses have genomes that are single-stranded RNA instead of DNA. These include the acquired immunodeficiency syndrome (AIDS) virus and some retroviruses that cause cancer. Here, an enzyme called reverse transcriptase converts the RNA genome of the virus into the DNA of the host cell genome, thus infecting the host. 

Gouet, R, et al. (1999). The highly ordered double-stranded RNA genome of bluetongue virus revealed by crystallography. Cell 97,481 90. 

Although any of these seven steps could be a druggable target, most of the antiviral agents clinically employed for non-AIDS infections act on the synthesis or assembly of either purines or pyrimidines (steps 3 and 4). For AIDS, reverse transcriptase inhibitors block transcription of the HIV RNA genome into DNA, thereby preventing synthesis of viral mRNA and protein protease inhibitors act on the synthesis of late proteins (steps 5 and 6). 

Primitive translation system develops, with RNA genome and RNA-protein catalysts... 

The catalytic and genetic roles of the early RNA genome were separated over time, with DNA becoming the genomic material and proteins the major catalytic species. 

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