Polyomaviruses are oncogenic in laboratory animals and can transform human cells in culture. Human polyomaviruses BK virus (BKV) and JC virus (JCV) commonly infect in childhood and remain latent in the infected host. The results of serologic studies with a lymphotrophic polyomavirus of African green monkeys (AG-LPV) imply the existence of a similar virus infection of man (human lymphotropic papovavirus -- H-LPV). The resources of the Johns Hopkins Oncology Center will be utilized in an attempt to isolate and characterize H-LPV and to examine the relationship of polyomaviruses to leukemias, lymphomas, pancreatic islet cell tumors and brain tumors. DNAs extracted from tumor tissues, urinary cells and peripheral leukocytes of patients will be screened by Southern transfer hybridization for sequences hybridizing with 32P-labeled AG-LPV, BKV,and JCV probes. Hybridizing viral genomes in the tissues will be characterized with respect to their copy numbers and state (integrated or free) and localized to specific cell types by in situ hybridization of paraffin sections with 35S-labeled probes. H-LPV genome will be cloned from human tissues which show sequences hybridizing with AG-LPV and transfected into susceptible lymphoid cell lines to produce infectious virus. Patients with acute lymphocyte leukemia (and other patients who have antibodies to H-LPV) will be monitored prospectively for changes in antibody titers, illnesses and the presence of H-LPV sequences in tumor tissues, peripheral leukocytes and urinary cells. Extracted DNAs from brain tumor tissues and paraffin sections of islet cell tumors will be examined for viral sequences. The patients whose tissues or cells are positive for virus will be studied clinically and for virus-related immunological response. BKV genomes from cancerous and non-cancerous tissues will be cloned and assayed for their ability to transform rodent cells. The possibility that variations in the regulatory region are responsible for differences in the transforming ability of the genomes will be examined by testing genomic constructs of BKV with different regulatory regions for their transforming ability. The regulatory regions of BKV genomes which contribute to the transforming abilities of BKV will be sequenced to identify genomic rearrangements which correlate with increased transforming ability. This combined virological and clinical study will help to determine the role, if any, of human polyomaviruses in the etiology of the malignancies examined.
