Isolation And Characterization Of Viral Nucleoprotein Complexes From Polyoma Virus Infected Mouse Kidney Cells

Expression of an immune response is the net result of complex synergisƯ tic and antagonistic activities performed by a variety of cell types. It includes macrophages, T and B populations which may interact in performance of a response, and suppressor cells interfering with it. Accordingly, a lack of resƯ ponse may not necessarily indicate absence of immunocompetent cells, but rather nonexpression of competence. Thus, one should consider two possible situations, which are by no means mutually exclusive, to account for immunoƯ logic unresponsiveness: (a) one or more of the cell populations composing the synergistic unit is absent or immature, and (b) an antagonistic unit which interferes with the response is dominating. In view of this, an approach to development of immune reactivity necessitates parallel surveys of development of cells with the potential to perform, as well as of cells which can suppress the response. Classification of the various cell types has been based so far on their phenotypic properties (e. g., membrane antigen markers, cell receptors, proƯ duction and secretion of immunoglobulins, etc.). Genotypically, T and B cells may represent either separate, independent cell lines, or different stages of development within the same cell lineage.

This book provides the most up-to-date review of the simian virus 40 (SV40) minichromosome as a model for the mammalian chromosome in studies of DNA replication. It focuses on disruption of DNA replication by anticancer drugs and DNA-damaging agents. There is a strong emphasis on the unique advantages of SV40 as an experimental system for the analysis of these classes of anticancer drug mechanisms. The new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication are covered in detail to aid readers in designing and interpreting similar experiments. Presents unique advantages of SV40 as an experimental system for the study of classes of anticancer drugs Details new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication Provides details to help the reader design and interpret similar experiments

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having only recently passed through its descriptive phase of naming and num bering, has probably reached that stage at which relatively few new truly new-viruses will be discovered. Triggered by the intellectual probes and techniq ues of molecular biology, genetics, biochemical cytology, and high-resolution microscopy and spectroscopy, the field has experienced a genuine information explosion. Few serious attempts have so far been made to chronicle these events. This comprehensive series, which will comprise some 6000 pages in a total of about 22 volumes, represents a commitment by a large group of active investigators to analyze, digest, and expostulate on the great mass of data relating to viruses, much of which is now amorphous and disjointed and scattered throughout a wide literature. I n this way, we hope to place the entire field in perspective as well as to develop an invaluable reference and sourcebook for researchers and students at all levels. This series is designed as a continuum that can be entered anywhere but which also provides a logical progression of developing facts and integrated concepts.

It has been more than twenty years since the isolation of polyoma virus and SV40, and the reports that they could produce tumors in animals and transformation of cells in culture. What was startling was that these biologic properties are associated with viruses that contain genetic in formation that is able to code for only five or six proteins. Since that time, investigations with these viruses have been in four principal areas. One major area of study has been on cells transformed by viruses that show altered growth properties and specify new viral and cellular proteins. Transformation studies have focused on the tumor (T) antigens that are specified by the virus and are required to initiate and to maintain the transformed state. Current studies on transformation are summarized in Chapter 4. The second broad area of investigation concerns replication of viruses during a lytic cycle of infection. T-antigens that are the hallmark of transformed cells are also expressed in cells that are lytically infected and are required for viral DNA replication and also function to alter rates of transcription of the early and late viral genes. Except for T-antigen, virus replication depends on the cellular enzymatic machinery and so the description of viral macromolecular synthesis has provided valuable insights into the cellular biosynthetic pathways. These studies are described in Chapters 1-3. The studies that have medical relevance concern JC and BK viruses and there is evidence of widespread exposure of human populations to these agents.

The impact of basic research on oncology has been particularly impressive in the recent search for the cause of malignancy. Equally impressive is our appreciation of the cause of tumors based on observation. Even in the earliest era of the study of infectious diseases, it was proposed that tumorous growth in animals and birds resulted from "minute" infectious particles. Experiments then supported the hypothesis, that the etiologic agent in many animal tumors was viral. The development of molecular biology, supported by technical advances and conceptual understanding of macromolecular action, led to an explosive increase in studies of animal oncogenic viruses. For a decade, new findings emerged from research laboratories revealing the enormous variety of such agents, the complex ity of their interactions with cells, and the tantalizingly possible mechanisms by which they might cause malignant transformation of the cell. Repeatedly, clues emerged which suggested the intervention of viral agents in human tumors. A breathless excitement pervaded both the scientific and public communities as highly publicized findings rapidly followed one another. The excitement was no less scientific than it was practical, for implicit in the concept of the viral oncogen is the possibility of specific virostatic or virotoxic agents or of immunization.