This project provides for continued investigations (previously supported by contract N01-CP-54338 and CP-91044, now being phased out) of type C RNA viruses spontaneously produced by human lymphoma cell lines established in this laboratory, in particular, SU-DHL-1, derived from a boy with a diffuse histiocytic lymphoma, and SU-AmB-3, derived from a child with ataxia-telangiectasia and an American Burkitt's lymphoma. The reverse transcriptase of each virus will be purified sequentially on poly rC-agarose and with a recently prepared monoclonal hybridoma antibody, and studied by tryptic digestion and high pressure liquid chromotography peptide mapping. The virion structural proteins will be isolated and characterized. Envelope glycoprotein (gp70) will be purified on lentil lectin columns and used to prepare monoclonal hybridoma antibodies for affinity column virus purification. The major internal core protein of 28,000 daltons (p28), identified in SU-DHL-1 and Su-AmB-3 with the aid of another monoclonal hybridoma antibody, will be peptide-mapped and partially sequenced. Synthetic oligodeoxynucleotides coding for these sequences will then be prepared by a method developed in the laboratory of Dr. Leroy Hood, and used as a probe to detect the corresponding intracellular viral mRNA sequences. Isolation of the intracellular viral RNA or proviral DNA genome will also be attempted by hybridization with woolly monkey virus (SSV-1) cDNA cloned in the plasmid-E. coli system. A radioimmunoassay using 125I-p28 and its hybridoma antibody is now being established to screen other lymphoma cell lines and to test for competing antibody in the sera of patients with similar types of lymphomas, leukemias, other neoplasms, and non-neoplastic conditions. The oncogenicity of these viruses will be tested by in vitro infection of simian bone marrow and peripheral blood cells and reimplantation into autologous hosts, which will then be observed for the development of hematologic neoplasia.