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Publisher Summary Identification of sequences from a new human herpesvirus in tumour tissue from AIDS-related Kaposi's sarcoma (KS) is done using the technique of Representational Difference Analysis (RDA). This technique uses cycles of polymerase chain reaction (PCR) and subtractive hybridization to amplify and enrich low-abundance DNA sequences present in only one of two otherwise identical DNA populations, and is therefore ideal for determining small differences between complex genomes. KS tumour usually appears as brownish-purple lesions, often on the extremities, but may in more aggressive forms of the disease progress to involve organs such as the lungs, lymph nodes, and gastrointestinal tract. The lesions contain many types of cell but are characterized histologically by the presence of elongated spindle cells and irregular slit-like vascular spaces. Seroepidemiology and PCR studies strongly suggest that HHV-8 is the cause of Kaposi's sarcoma and primary effusion lymphoma, and is also associated with multicentric Castleman's disease. Although HHV-8 has not yet been shown to be a transforming virus in vitro, the virus encodes several proto-oncogenes capable of the deregulation of cell cycle control, inhibition of apoptosis and control of growth differentiation, which could contribute to tumour formation.

Publisher Summary This chapter analyzes the interrelationships between Epstein-Barr herpes virus (EBV) and primates other than man. It also discusses the aspects of the discovery of the virus, its association with Burkitt lymphoma, infectious mononucleosis, and nasopharyngeal carcinoma, and its biologic properties studied in vitro . The studies of EBV in nonhuman primates have been useful in many respects. They have provided clues about the evolution of this highly adapted human parasite. Infection of nonhuman primate cells in vitro has yielded a regular source of cell-free virus for laboratory studies and has also clearly demonstrated the importance of host-specified control mechanisms in the regulation of the expression of viral information in transformed cells. The experimental infection of primates was successful once adequate amounts of transforming virus were available and once the virus host range was better defined by the means of in vitro transformation. Subsequent study allowed a direct demonstration of the capacity of EBV to cause lymphoreticuloproliferative disease. The identification of susceptible primate hosts now offers promise of the detailed analysis of the pathogenesis of EBV-induced disease and of the comparison of the pathogenic properties of different EBV-related viruses.

Publisher Summary The isolation and characterization of mutants of viruses that infect bacterial and animal cells has led to increased understanding of viral genetic functions. This approach has been increasingly used in avian and mammalian systems in attempts to determine the number and actions of genes that mediate the transforming activities of oncogenic viruses. The methods used in mammalian systems to obtain virus mutants have usually involved mutagenization of virus, and screening systems have generally been designed to detect conditional lethal effects. DNA and RNA tumor viruses that nonproductively transform and become stably associated with the cell have provided another approach with which to study both viral and cellular genes involved in the expression of viral transformation. Selection systems devised to enhance survival of revertant clones of virus transformed parental cells have yielded both temperature dependent and independent revertants that express normal growth properties in vim and in vivo, and yet still contain the transforming virus. This chapter describes selection techniques that have been developed for the isolation of morphological revertants of tumor virus-transformed cells and characterization of their biological properties. The techniques described here are also applicable to the isolation of revertants of other carcinogen-induced, virus-transformed or spontaneously transformed tumor cells. These MSV transformed nonproducer cell revertants should be of use in developing a better understanding of the virus-cell interactions involved in transformation.

Publisher Summary This chapter evaluates the available knowledge of simian virus 40 (SV40) oncogenesis and assesses the implications for carcinogenesis by DNA-tumor viruses as a whole. It summarizes different tests that can be employed to detect virus-induced changes in SV40-transformed cells. Inoculation of such cells into susceptible hosts usually results in the production of tumors, the ultimate criterion necessary to establish that malignant transformation has indeed occurred. Fusion or cocultivation of the transformed cell with normal susceptible cells may sometimes succeed in the rescue of infectious virus. The optimum conditions required to elicit the production of virus from a majority of the transformed cells have not yet been established. Transformed cells are usually immune to superinfection by the transforming virus. Nucleic acid hybridization experiments indicate that multiple copies of the SV40 genome is present, probably integrated into the host cell chromosome. Virus-specific mRNA is present in the transformed cells. The extent of the transcription of the viral genome seems to vary from one transformed cell line to the next. No relationships have been established between the extent of transcription in a given transformed cell line and the number and/or magnitude of virus-specific changes of that cell line. A series of in vitro tests may detect a variety of surface changes on the transformed cells. These tests include immunofluorescence, agglutination, cytotoxicity, colony inhibition, and mixed hemadsorption.