Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 138

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		Flaviviridae Picornaviridae	1111	21, 22
Nested mRNAs		Coronaviridae Arteriviridae	66	5, 65, 6

Figure 3.10 Information retrieval from viral genomes. Different strategies for decoding the information in viral genomes are depicted. CBF, CCAAT-binding factor; USF, upstream stimulatory factor; IRES, internal ribosome entry site.

The utility of viral genome sequences extends well beyond building a catalog of viruses. These sequences are the primary basis for classification and also provide information on the origin and evolution of viruses. In outbreaks or epidemics of viral disease, even partial genome sequences can provide information about the identity of the infecting virus and its spread in different populations. New viral nucleic acid sequences can be associated with disease and characterized even in the absence of standard virological techniques (Volume II, Chapter 10). For example, human herpesvirus 8 was identified by comparing sequences present in diseased and nondiseased tissues, and a novel member of the parvovirus family was identified as the cause of unexpected deaths of laboratory mice in Australia and the United States.

Despite their utility, genome sequences cannot provide a complete understanding of how viruses reproduce. The genome sequence of a virus is at best a biological “parts list”: it provides some information about the intrinsic properties of a virus (for example, predicted sequences of viral proteins and particle composition), but says little or nothing about how the virus interacts with cells, hosts, and populations. This limitation is best illustrated by the results of environmental metagenomic analyses, which reveal that the number of viruses around us (especially in the sea) is astronomical. Most are uncharacterized and, because their hosts are also unknown, cannot be investigated. A reductionist study of individual components in isolation provides few answers. Although the reductionist approach is often the simplest experimentally, it is also important to understand how the genome behaves among others (population biology) and how the genome changes with time (evolution). Nevertheless, reductionism has provided much-needed detailed information for tractable virus-host systems. These systems allow genetic and biochemical analyses and provide models of infection in vivo and in cells in culture. Unfortunately, viruses and hosts that are difficult or impossible to manipulate in the laboratory remain understudied or ignored.