MALIGNANT-LYMPHOMA INDUCTION OF RABBITS WITH ORAL SPRAY OF EPSTEIN-BARR VIRUS-RELATED HERPESVIRUS FROM SI-IIA CELLS (HTLV-II-TRANSFORMED CYNOMOLGUS CELL-LINE) - A POSSIBLE ANIMAL-MODEL FOR EPSTEIN-BARR-VIRUS INFECTION AND SUBSEQUENT VIRUS-RELATED TUMORS IN HUMANS

Malignant lymphoma (ML) was induced in eight of nine rabbits inoculate d by oral spray of the cell-free pellets from Si-IIA culture (HTLV-II- transformed leukocyte cell line of the Cynomolgus-producing Epstein-Ba rr virus (EBV)-related herpesvirus) after 64-141 days. None of the rab bits inoculated with EBV from B-95-8 cells or HTLV-II from MOT cells d eveloped ML. Malignant lymphomas were usually of diffuse, large-cell o r mixed type. HTLV-II infection was excluded by the polymerase chain r eaction (PCR) and the particle agglutination test. EBV-encoded RNA-1 a nd EBV-related DNA were detected in the tumor tissues by in situ hybri dization and PCR, respectively. Anti-viral capsid antigen of EBV antib ody (anti-VCA) was observed 3 weeks after oral inoculation of Si-IIA c ell-free pellets. Polymerase chain reaction revealed continuous detect ion of EBV-related virus DNA in the peripheral blood leukocytes from 3 days after oral inoculation. These results show that ML induced orall y with Si-IIA cell-free pellets was caused by EBV-related herpesvirus harbored by Si-IIA cells. Oral spray of EBV from B-95-8 also induced E BV infection in rabbits, which was confirmed both by the presence of a nti-VCA and by PCR. These oral infection and malignant lymphoma induct ion systems of rabbit using EBV-related virus from Si-IIA or human EBV are useful animal models for the study of EBV infection and EBV-relat ed lymphomas in humans.