Herpesvirus saimiri-induced lymphoblastoid rabbit cell line: growth characteristics, virus persistence, and oncogenic properties

Abstract

A nonproducer lymphoblastoid cell line (7710) containing the herpesvirus saimiri (HVS) genome was established from the HVS-positive spleen of a male, inbred New Zealand White rabbit (III/J strain) which had developed a well-differentiated lymphoma after inoculation of HVS and 12-O-tetradecanoylphorbol-13-acetate (TPA). Antibodies to HVS early and late antigens were detected in the serum of rabbit 7710 by indirect immunofluorescence and immunoprecipitation. The cell line was of T-cell origin, did not produce HVS, and could not be superinfected with HVS. However, HVS early antigens could be induced in the cells with n-butyric acid and TPA or TPA alone. On the other hand, late antigens were never observed, and infectious virus could not be rescued by cocultivation of 7710 cell with OMK cells. The 7710 cells were T-cell growth factor dependent, even after many in vitro passages. The 7710 cell line contained multiple copies of a nonintegrated, covalently closed circular HVS genome. As is characteristic of some other HVS-transformed nonproducer lymphoid cell lines, a large segment of unique light (L) DNA was missing in the persistent circular viral DNA present in 7710 cells. This deletion spanned at least 42.5 kilobases, corresponding to the segment between 12.3 and 50.7 map units of full-length, infectious virion L-DNA. The 7710 cells failed to induce tumors in athymic nude mice, but inbred rabbits inoculated with as few as 100 of these cells developed fatal lymphomas. Chromosomal analysis showed that tumors were due to the growth of donor cells. Cells recovered from one of the rabbits inoculated with 7710 cells also contained HVS DNA and, after in vitro culture, induced the same type of lymphoma when inoculated into two other III/J-strain rabbits. None of the previously described HVS-transformed cell lines have been able to induce tumors in either their host species or nude mice. Thus, our demonstration that the 7710 cell line is readily transplantable in syngeneic rabbits represents the first available model which allows analysis of many biological and molecular aspects of the in vivo oncogenicity of HVS.