4 Structure of the Retroviral Genome

Abstract

I. INTRODUCTION At the time of the previous edition of this work (Tooze 1973), virtually nothing was known about the organization of the genomes of retroviruses; even their size was a matter of speculation. In the intervening years, a great deal of methodological power was brought to bear on this problem, with the result that we can now describe in great detail the arrangement of coding and noncoding sequences and, to a lesser extent, how they interact in virus replication and transformation. Because the most detailed information is available for the Rous sarcoma and avian leukosis viruses (RSV and ALV) and the murine leukemia viruses (MLV), this discussion will center on these groups, with other retroviruses introduced when appropriate for comparative purposes. Ultimately, all effects of virus infection on a cell can be ascribed to interactions of the viral genome and its products with the machinery of the host cell. The genome of a retrovirus is relatively small, yet it displays a number of features unique to this virus group, including:replication involving a proviral DNA intermediate, which subsequently becomes integrated into the host-cell genome and serves as a template for viral mRNA transcription by the host cell’s RNA synthetic and processing systems; a very high frequency of intermolecular recombination between related viruses; an ability to acquire new genes that encode functions responsible for neoplastic transformation of the host cell; and close relationship to endogenous proviruses in the cellular DNA of uninfected animals, which are passed...