What Do Viral Genomes Look Like?

Some small RNA and DNA genomes enter cells from virus particles as naked molecules of nucleic acid, whereas others are always associated with specialized nucleic acid-binding proteins. A fundamental difference between the genomes of viruses and those of hosts is that although viral genomes are often covered with proteins, they are usually not bound by histones (polyomaviral and papillomaviral genomes are an exception.

While viral genomes are all nucleic acids, they should not be thought of as one-dimensional structures. Virology textbooks (this one included) ofen draw genomes as straight, one-dimensional lines, but this notation is for illustrative purposes only; physical reality is certain to be dramatically different. Genomes have the potential to adopt amazing secondary and tertiary structures in which nucleotides may engage in long-distance interactions ( Te sequences and structures near the ends of viral genomes are ofen indispensable for viral replication.

For example, the DNA sequences at the ends of parvovirus genomes form T-shaped structures that are required for priming during DNA synthesis. Proteins covalently attached to 5 ends, inverted and tandem repeats, and tRNAs may also participate in the replication of RNA and DNA genomes. Secondary RNA structures may facilitate translation (the internal ribosome entry site [IRES] of picornavirus genomes) and genome packaging (the structured packaging signal of retroviral genomes).

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, 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.

Viral genome sequences have many uses, including classification of viruses. Furthermore, sequence analysis has identified many relationships among diverse viral genomes, providing considerable insight into the origin of viruses. A great deal can also be learned from the lack of such relationships: 93% of the 2,500 genes of Pandoravirus salinus resemble nothing known. Consequently, their origin cannot be traced to any known cellular lineage, leading to the controversial suggestion that these giant viruses are derived from a now-extinct fourth domain of life. 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.

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