MALIGNANT-LYMPHOMA INDUCTION IN RABBITS BY INTRAVENOUS INOCULATION OFEPSTEIN-BARR-VIRUS-RELATED HERPESVIRUS FROM HTLV-II-TRANSFORMED CYNOMOLGUS LEUKOCYTE CELL-LINE (SI-IIA)

Malignant lymphomas, which were usually of T-cell type, were induced i n 10 of 13 (77%) male rabbits (Japanese white, 8/10; New Zealand white , 2/3) inoculated i.v. with HTLV-II-transformed simian (Cynomolgus) le ukocyte cell line (SI-IIA) cells. Of 7 rabbits injected with cell-free pellets from Si-IIA cultures, 5 also developed malignant lymphoma (15 -28 days), Lymphoma development was completely inhibited by inactivati on of cell-free pellets from Si-IIA culture with ethyl ether and was a lmost suppressed by neutralization of the cell-free pellets with anti- Si-IIA sera. Herpesvirus particles were discovered very rarely in Si-I IA cells, in addition to C-type virus particles, by electron microscop y. Si-IIA cells were positive for Epstein-Barr-virus(EBv)-associated n uclear antigen (EBNA) by immunofluorescence (IF) test. Antibody respon se to viral capsid antigen of EBV was also detected in sera from rabbi ts inoculated with Si-IIA. EBV-encoded RNA-I (EBER-I) was demonstrated in Si-IIA, the tumor tissues and all rabbit tumor cell lines by in si tu hybridization. EBV DNA was also detected in SI-IIA and rabbit lymph oma cell lines by polymerase chain reaction (PCR) and Southern blottin g, However, EBV DNA was amplified only by some primers complementary t o human EBV sequence (B95-8), but not by other primers. Integration of HTLV-H provirus genome could not be detected in Si-IIA-induced rabbit tumor cells, Moreover, no lymphoma was induced by inoculation of HTLV -IIC and MOT (other HTLV-II-producing human cell lines), B95-8 (EBV-pr oducing cell line) or TALL-I and peripheral leukocytes from normal Cyn omolgus (controls), Neither Herpesvirus saimiri nor H. ateles (simian oncogenic viruses) were detected in Si-IIA cells by IF test. These dat a suggest that the high rate of lymphoma induction in rabbits may not be caused by HTLV-II, human EBV (B95-8) or well-known simian oncogenic viruses, but by EBV-related herpesvirus derived from Si-IIA cells or HTLV-HA cells, with which Si-IIA was established. The availability of this animal model promises to clarify the role of EBV in human lymphom a and provides a means of studying prophylactic and therapeutic regime ns. (C) 1995 Wiley-Liss, Inc.