Cyno-EBV (EBV-related herpesvirus from cynomolgus macaques) induces rabbitmalignant lymphomas and their tumor cell lines frequently show specific chromosomal abnormalities

Malignant lymphoma (ML) induction in rabbits by Epstein-Barr virus (EBV)-re lated herpesvirus of cynomolgus (Cyno-EBV) is reported. Twenty-seven of 30 (90%) rabbits inoculated intravenously with Cyno-EBV-producing simian (cyno molgus) lymphocyte cell line (Ts-B6) cells developed ML between 45 and 115 days after inoculation. The peroral inoculation of Ts-B6 cells induced ML i n only 2 of 10 (20%) rabbits (75 to 85 days). Five of 6 (83%) rabbits injec ted with cell-free pellets from Ts-B6 cultures also developed ML (27 to 122 days). Antibody response to the viral capsid antigen of EBV was also detec ted in sera from rabbits inoculated with Ts-B6. ML of the large cell or mix ed type infiltrated diffusely in many organs, frequently involving the sple en, liver, kidneys, heart, and less frequently the lungs, lymph nodes, brai n, eyes, gastrointestinal tract, thymus, and bone marrow. A chromosomal ana lysis of five lymphoma cell lines established from tumor-bearing rabbits re vealed the rabbit karyotype. Three of these cell lines showed the chromosom al abnormalities with 12q- or t (7p+:12q-). EBV-encoded small RNA-1 and EBV -associated nuclear antigen 1 were expressed in Ts-B6 cells, the tumor tiss ues, and all rabbit cell lines by in situ hybridization and by immunofluore scence tests, respectively. EBV DNA was also detected in Ts-B6 cells and ra bbit lymphoma cell lines by polymerase chain reaction and Southern blot ana lysis. The Southern blots of EBV termini revealed oligoclonal bands in the Cyno-EBV-induced rabbit lymphomas. No lymphoma was induced by the inoculati on of B95-8 (EBV-producing cells) or peripheral leukocytes from normal cyno molgus (controls). These data suggest that the high rate of lymphoma induct ion in rabbits may be caused not by human EBV (B95-8) but by Cyno-EBV from Ts-B6 cells. A sequence analysis of the IR1 (BamHIW) region of Cyno-EBV rev ealed that this region is quite similar to that of herpesvirus Macaca fasci cularis 1,which is a causative agent for a monkey model of AIDS-retated lym phomas. The present rabbit model of lymphoma with specific chromosomal abno rmalities is very useful to clarify the role of EBV in human EBV-associated lymphoma and provides a means for studying prophylactic and therapeutic re gimens.