Brad Ozanne

Viral DNA sequences in cells transformed by simian virus 40, adenovirus type 2 and adenovirus type 5.

Until recently, the study of DNA tumor viruses has been an essentially syntactic subject. Those who have worked in the field commonly believe, for example, that there are interconnections between the expression of integrated viral genomes, the structure of cell surfaces and the growth properties of cells. On the whole, however, the anastomosis of various features has worked out well: it has resulted in a groundplan on which the apparently diverse elevations of a fast-growing field can quickly be sited with respect to one another.

Characterization of SV40 DNA Rescued from Transformed Mouse Cells

It seems evident that in SV40-transformed mouse cells the viral DNA has combined with the host chromosomal DNA to form a stable integrated unit (Sambrook et al. 1968). We have been interested in the specificity of integration and the mechanism of insertion of viral sequences.

Studies on the Transcription of Simian Virus 40 and Adenovirus Type 2

Both adenovirus 2 and simian virus 40 interact with cultured cells in two different ways. On the one hand, there is a productive or lytic response in which the great majority of the cells yield progeny virus and die, and on the other there is an incomplete infection in which little or no virus is produced and the cells survive. Some of these surviving cells assume a new set of stable properties that closely resemble the properties of cells derived from tumors. These cells are said to be “transformed.” Which consequence virus infection produces is solely determined by the species of the host cell. Table I lists the cells that are commonly used in studies of lytic infection and transformation by adenovirus 2 and SV40.

Transcription of SV40 in Lytically Infected and Transformed Cells

As long as we take reasonable care, we can grow stocks of Simian Virus that are remarkably homogeneous. Each infectious particle contains a single molecule of DNA weighing 3.4 x 106 daltons—enough to code for perhaps 5–8 polypeptides of average size. The manner in which this virus-coded information is expressed is highly cell-dependent. For example, after infection with SV40, monkey cells undergo a productive or lytic response, during which there is an ordered appearance of virus-specific functions, with some virus products present at all times and others detectable only in the late stages of the viral growth cycle. The infection progresses through a well-defined series of episodes, which culminate in cell death and the concomitant liberation of a new crop of virus particles. The events are multiplicity-independent in that they occur in the same order, albeit at different rates, in cells infected either with one infectious particle or with a hundred. By contrast, the outcome of exposing mouse cells to SV40 is very different.