Principles of Virology. Jane Flint
Genome structures in cartoons and in real life. (A) Linear representation of a picornavirus RNA genome. UTR, untranslated region. (B) Long-distance RNA-RNA interactions in a tombusvirus RNA genome. The 4,252-nucleotide viral genome is shown with secondary RNA structures at the 5′ and 3′ ends. Sequences that base-pair are shown in blue (required for RNA frameshifting) and red (required to bring ribosomes from the 3′ end to the 5′ end). Courtesy of Anne Simon, University of Maryland. (C) Schematic representation of RNA secondary-structure elements in the human immunodeficiency virus type 1 5′ leader, including the core packaging signal. (D) NMR structure of the RNA shown in C, without elements colored black. Courtesy of Paul Bieniasz, Rockefeller University.
Coding Strategies
The compact genome of most viruses renders the “one gene, one mRNA” dogma inaccurate. Extraordinary tactics for information retrieval, such as the production of multiple subgenomic mRNAs, alternative mRNA splicing, RNA editing, and nested transcription units (Fig. 3.10), allow the production of multiple proteins from a single viral genome. Further expansion of the coding capacity of the viral genome is achieved by posttranscriptional mechanisms, such as polyprotein synthesis, leaky scanning, suppression of termination, and ribosomal frameshifting. In general, the smaller the genome, the greater the compression of genetic information.
What Can Viral Sequences Tell Us?
Knowledge about the physical nature of genomes and coding strategies was first obtained by the study of the nucleic acids of viruses. Indeed, DNA sequencing technology was perfected on viral genomes. The first genome of any kind to be sequenced was that of the Escherichia coli bacteriophage MS2, a linear ssRNA of 3,569 nucleotides. dsDNA genomes of larger viruses, such as herpesviruses and poxviruses (vaccinia virus), were sequenced completely by the 1990s. Since then, high-throughput sequencing has revolutionized the biological sciences, allowing rapid determination of genome sequences from clinical and environmental samples. Organand tissue-specific viromes of many organisms have been determined. In one study, over 186 host species representing the phylogenetic diversity of vertebrates, including lancelets (chordates, but considered invertebrates), jawless fish, cartilaginous fish, ray-finned fish, amphibians, and reptiles, all ancestral to birds and mammals, were sampled. RNA was extracted from multiple organs and subjected to high-throughput sequencing. Among 806 billion bases that were read, 214 new viral genomes were identified. The results show that in vertebrates other than birds and mammals, RNA viruses are more numerous and diverse than suspected. Every viral family or genus of bird and mammal viruses is also represented in viruses of amphibians, reptiles, or fish. Arenaviruses, filoviruses, and hantaviruses were found for the first time in aquatic vertebrates. The genomes of some fish viruses have now expanded so that their phylogenetic diversity is larger than in mammalian viruses. New relatives of influenza viruses were found in hagfish, amphibians, and ray-finned fish. As of this writing, the complete sequences of >8,000 different viral genomes have been determined. Published viral genome sequences can be found at http://www.ncbi.nlm.nih.gov/genome/viruses/.
| Mechanism | Diagram | Virus | Chapter(s) | Figures in appendix |
|---|---|---|---|---|
| MultiplesubgenomicmRNAs |
|
Adenoviridae Hepadnaviridae Herpesviridae Paramyxoviridae Poxviridae Rhabdoviridae | 7, 87, 107676 | 1, 211, 1217, 1825, 2631, 32 |
| Alternative mRNA splicing |
|
Adenoviridae Orthomyxoviridae Papillomaviridae Polyomaviridae Retroviridae | 7, 887, 8810 | 1, 215, 1623, 2429, 30 |
| RNA editing |
|
Paramyxoviridae Filoviridae Hepatitis delta virus | 6, 888 | |
| Information on both strands |
|
Adenoviridae Polyomaviridae Retroviridae | 7-97-910 | 1, 223, 2429, 30 |
| Polyproteinsynthesis |
|
AlphavirusesFlaviviridae Picornaviridae Retroviridae | 6, 116, 116, 116, 11 | 33, 349, 1021, 2229, 30 |
| Leaky scanning |
|
Orthomyxoviridae Paramyxoviridae Polyomaviridae Retroviridae | 11111111 | 15, 1629, 30 |
| Reinitiation |
|
Orthomyxoviridae Herpesviridae | 1111 | 15, 16 |
| Suppression of termination |
|
AlphavirusesRetroviridae | 1111 | 33, 3429, 30 |
| Ribosomalframeshifting |
|
Astroviridae Coronaviridae Retroviridae | 111111 | 5, 629, 30 |
| IRES |
|