Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 263

The genomes of RNA viruses may be unimolecular or segmented; single stranded of (+), (−), or ambisense polarity; double stranded; or circular. These structurally diverse viral RNA genomes share a common requirement: they must be copied efficiently within the infected cell to provide both genomes for assembly into progeny virus particles and messenger RNAs (mRNAs) for the synthesis of viral proteins. The production of these RNA molecules is a unique process that has no parallel in the cell. The genomes of all RNA viruses except retroviruses and hepatitis delta virus encode an RNA-dependent RNA polymerase (RdRP) (Box 6.1) to catalyze the synthesis of new genomes and mRNAs.

Virus particles that contain (−) strand or double-stranded RNA genomes must contain the RdRP, because the incoming viral RNA can be neither translated nor copied by the cellular machinery. Consequently, the deproteinized genomes of (−) strand and double-stranded RNA viruses are not infectious. In contrast, viral particles containing a (+) strand RNA genome lack a viral polymerase; the deproteinized RNAs of these viruses are infectious because they are translated in cells to produce, among other viral proteins, the viral RNA polymerase. An exception is the retrovirus particle, which contains a (+) stranded RNA genome that is not translated but rather copied to DNA by reverse transcriptase (Chapter 10).

The mechanisms by which viral mRNA is made and the RNA genome is replicated in cells infected by RNA viruses appear even more diverse than the structure and organization of viral RNA genomes (Fig. 6.1). Nevertheless, each mechanism of viral RNA synthesis meets two essential requirements common to all infectious cycles: (i) during replication, the RNA genome must be copied from one end to the other with no loss of nucleotide sequence; and (ii) viral mRNAs that can be translated efficiently by the cellular protein synthetic machinery must be made.

In this chapter, we consider the mechanisms of viral RNA synthesis, the switch from mRNA production to genome replication, and the origins of genetic diversity. Much of our understanding of viral RNA synthesis comes from experiments with purified components. Because it is possible that events proceed differently in infected cells, the results of such in vitro studies are used to build models for the different steps in RNA synthesis, which must then be tested in vivo. While many models exist for each reaction, those presented in this chapter were selected because they are consistent with experimental results obtained in different laboratories or have been validated with simplified systems in cells in culture. The general principles of RNA synthesis deduced from such studies are illustrated with a few viruses as examples.