BENIGN AND MALIGNANT SMOOTH-MUSCLE TUMORS CONTAINING EPSTEIN-BARR-VIRUS IN CHILDREN WITH AIDS

Smooth muscle tumors (leiomyosarcomas) are the second most prevalent m alignancy of children with the acquired immunodeficiency syndrome (AID S). We have investigated the tumors, plasma, and peripheral white bloo d cells of eight children with AIDS with smooth muscle tumors for evid ence of tumor association with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV). Very low levels of HIV were found in the tum ors of the AIDS patients, probably resulting from blood-borne carriage of virus. These smooth muscle tumors had very high quantities of EBV in all the tumor cells by in situ hybridization, with an average of 4. 5 EBV genomes per cell by quantitative polymerase chain reaction ampli fication. Increased amounts of EBV were found in the peripheral blood cells of two AIDS patients before the time of tumor diagnosis. EBV clo nality studies demonstrated different monoclonal EBV infection of two separate colonic tumors from one patient, and dual or mixed monoclonal EBV infection in another patient. The muscle cells of leiomyomas and leiomyosarcomas of patients with AIDS demonstrated prominent staining with antibodies to the EBV receptor. The uniform distribution and stri king amount of EBV in the tumor cells demonstrates that EBV is capable of infecting smooth muscle cells and that these cells support EBV rep lication. Clonal EBV proliferation suggests that EBV infection occurs at an early stage of tumor development. These findings indicate that E BV has a causal role in the oncogenesis of leiomyosarcomas of patients with AIDS.