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 inoculated by oral spray of the cell-free pellets from Si-IIA culture (HTLV-II- transformed leukocyte cell line of the Cynomolgus-producing Epstein-Barr virus (EBV)-related herpesvirus) after 64-141 days. None of the rabbits inoculated with EBV from B-95-8 cells or HTLV-II from MOT cells developed ML. Malignant lymphomas were usually of diffuse, large-cell or mixed type. HTLV- II infection was excluded by the polymerase chain reaction (PCR) and the particle agglutination teat. EBV-encoded RNA-1 and EBV-related DNA were detected in the tumor tissues by in situ hybridization and PCR, respectively. Anti-viral capsid antigen of EBV antibody (anti-VCA) was observed 3 weeks after oral inoculation of Si-IIA cell-free pellets. Polymerase chain reaction revealed continuous detection of EBV-related virus DNA in the peripheral blood leukocytes from 3 days after oral inoculation. These results show that ML induced orally 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 EBV infection in rabbits, which was confirmed both by the presence of anti-VCA and by PCR. These oral infection and malignant lymphoma induction 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-related lymphomas in humans.