Association of Simian Virus 40 with Rodent and Human Mesotheliomas

Abstract

Simian virus 40 (SV40) is an oncogenic papovavirus capable of inducing tumors in hamsters and of transforming cells from many species in tissue culture.(1) In the past, although useful for basic studies, the SV40-induced hamster tumor model was considered to have only limited relevance in the elucidation of mechanisms for human cancer development. Recently, however, the discovery of relationships between SV40 proteins and human tumor suppressor gene products suggested that DNA tumor viruses could possibly illuminate molecular mechanisms of human carcinogenesis.(2) Moreover, the very recent finding of SV40-like sequences in human tumors(3,4) underscores the direct relevance of SV40 research to human cancer. The SV40 proteins associated with in vivo oncogenesis and in vitro cell transformation are encoded by the early region of the virus; these proteins are known as the T (tumor) antigens because animals bearing tumors induced by SV40 have antibodies against these viral proteins. Two SV40 tumor antigens are detected in infected or transformed cells, “large T antigen” (Tag) and “small t antigen” (tag), and these two proteins are produced from a single viral gene by differential splicing of an RNA transcript.(1,2) Unlike the oncogenes of the retroviruses, the T antigen oncogenes of SV40 do not have a homologous cellular protooncogene.(5)