Differential ability of two simian virus 40 strains to induce malignancies in weanling hamsters

Abstract

Different strains of simian virus 40 (SV40) exist and are associated with some human malignancies, but it is not known if SV40 strains differ in biological potential in vivo. In two long-term experiments, Syrian golden hamsters 21 days of age were inoculated by the intraperitoneal route with two different strains of SV40 (10 7 plaque-forming units/animal) and were followed for 8 or 12 months. In vivo responses to strain VA45–54, isolated originally from monkey kidney cells, and to strain SVCPC, recovered from human cancers, were compared. Control animals of the same age were inoculated intraperitoneally with cell culture media. Malignancies developed only in animals infected with SV40 and not in controls. The rate of tumor development was more frequent among animals infected with strain SVCPC than with VA45–54, both in experiments held for 8 months (11/22, 50% vs. 4/20, 20%) and for 12 months (7/15, 47% vs. 3/13, 23%). Histologically, the tumors resembled mesotheliomas, osteosarcoma, and poorly differentiated sarcomas. Metastases to lung and lymph nodes occurred with both viral strains. T-antigen expression was detected in most tumor cells by immunohistochemistry. Anti-T-antigen antibodies were produced by almost all tumor-bearing animals and by about two-thirds of those that did not develop tumors after virus inoculation. SV40 viral neutralizing antibodies were detected in all tumor-bearing animals and in 92% and 38% of those inoculated with SVCPC and VA45–54, respectively, that failed to develop tumors. Antibody titers were usually higher in animals with tumors than in those without. Control animals did not develop viral antibodies. Infectious virus was recovered from 2 of 15 tumors tested. This study showed that there are biological differences between these two SV40 strains that influence the outcome of infections in normal hosts, including the development of malignancies and neutralizing antibody, and proved the principle that SV40 strains from different clades can vary in biological properties in vivo.