The United States is now experiencing an alarming increase in the frequency of cases of acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma (KS) in selected groups of the population suggesting an infectious etiological agent. The course of disease is aggressive and results in death within two years following diagnosis in 100 percent of AIDS patients and 80 percent of patients whose AIDS is manifested as Kaposi's sarcoma; The clustering of cases seen in Africa strongly resembles that of Burkitt's lymphoma, a cancer with known Epstein-Barr virus (EBV) involvement. AIDS is very often found in patients with active infections with cytomegalovirus (CMV), a virus related to EBV. however, the long-standing prevalence of CMV infection in the absence of disease argues against it as a primary etiological factor, yet no other candidate infectious agents have been identified. A course of experimentation is proposed which aims at the identification of genes involved in the malignant character of KS tumor cells and the potentially malignant lymph node cells in early stages of AIDS. Toward this end, we will: utilize in vitro assays for DNA-mediated cell transformation to recognize then isolate genes presumptively involved in in vivo transformation; analyze the state of integration, arrangement and expression of known virus genetic information and human endogenous retrovirus-like sequences; analyze the arrangement and expression of known potential human oncogenes, and finally; isolate tumor cell specific RNA transcripts. In this manner we hope to identify common genetic changes in cells of KS and AIDS patients and learn whether those changes result from alterations of normal cellular gene information, or are due to the acquisition of exogenous genetic information, or both. These experiments should shed light on the genetic basis for cell transformation in acquired immunodeficiency syndrome and Kaposi's sarcoma and possibly identify the etiological agent.
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