While several classes of viruses form stable associations with their hosts by integrating one or more copies of their genomes into the host cell DNA, retroviruses provide a unique and important system for the study of integrative recombination. Retroviral genomes are integrated with high efficiency at specific sites within the viral genome, but at a large number of sites in the host chromosome. Often a consequence of this integration event is a readily detectable change in cell growth. Modern methods of molecular cloning and analysis allow for the detection and amplification of rare DNA sequences such as an integrated viral segment. Molecular clones of several newly integrated retroviral genomes were produced in either plasmid or bacteriophage cloning vehicles using recombinant DNA techniques and were characterized using electron microscope heteroduplex and R-loop methods. Detection of sequence homology even when interrupted by intervening cellular DNA is often accurately mappable in the electron microscope using these methods. These studies have not only shown the arrangement of integrated viral sequences within infected host cell DNA, but have also demonstrated the presence and sequence arrangement of certain viral transforming sequences within normal, uninfected host cells as well. Unique inverted repeat sequences structurally resembling bacterial transposable elements have been identified and molecularly cloned. The major objective of these studies has been the application of physical and biochemical techniques to assess the influence of integrative position or flanking cellular sequences on subsequent viral function and to define in molecular terms those events which take place during integrative recombination in eukaryotic cell systems.
