MALIGNANT-LYMPHOMA INDUCTION IN RABBITS BY ORAL INOCULATION OF CRUDE VIRUS FRACTION PREPARED FROM TS-B6 CELLS (CYNOMOLGUS B-LYMPHOBLASTOID CELLS HARBORING EPSTEIN-BARR VIRUS-RELATED SIMIAN HERPESVIRUS)

Malignant lymphoma was induced in Japanese (JWY), New Zealand (NZY) an d Dutch (DUY) white rabbits by oral spray of cell-free pellets of cult ure fluid (crude virus fraction) of Ts-B6 cells (cynomolgus monkey B-l ymphoblastoid cells harboring Epstein Barr virus-related simian herpes virus or Cyno-EBV). Nine of 11 inoculated rabbits developed malignant lymphomas within 42-160 days after oral inoculation (JWY, 2/3; NZY, 5/ 6; DUY, 2/2). In contrast, none of the control rabbits inoculated in t he same fashion with B95-8 (EBV-producing marmoset cell line) cell-fre e pellets developed malignant lymphoma. Most rabbits showed increased anti-VCA IgG and anti-EA-DR IgG antibody titers after inoculation by o ral spray of Ts-B6 cell-free pellets. EBV-encoded RNA-1 was revealed i n the tumor cells by in situ hybridization. EBV DNA was detected in th e rabbit peripheral blood leukocytes (PBL) by polymerase chain reactio n; the earliest positive result was obtained only two days after oral inoculation. These data suggest that orally administered Cyno-EBV in T s-B6 cells infects PBL and then induces malignant lymphoma in rabbits. The availability of this animal model promises to clarify the role of EBV in human lymphoma and provides a means for studying prophylactic and therapeutic regimens.