Epithelial tumours induced by a herpesvirus oncogene in transgenic mice.

To investigate the role of herpesviral genes in tumourigenesis, transgenic mice were generated expressing STP-C, a transformation associated protein of the lymphoma inducing herpesvirus saimiri. Epithelial tumours developed in the salivary gland, pancreas, thymus and liver of transgenic mice within the first weeks of life. Thus, the target cells for tumour formation in the transgenic mice were surprisingly different from those of the herpesvirus from which the oncogene was derived. Our results identify STP-C as a herpesvirus oncogene sufficient for tumour induction without the cooperation of other viral gene products. Furthermore, the results demonstrate pleiotropic transforming capabilities of the STP-C oncogene and suggest that the specificity of lymphoma induction by the virus is determined by factors other than the oncogene itself.

Identification of transforming genes of subgroup A and C strains of Herpesvirus saimiri.

Herpesvirus saimiri is an oncogenic herpesvirus that induces rapidly progressing lymphomas in New World primates. Using retrovirus vectors for gene transfer, specific open reading frames of H. saimiri were tested for their ability to transform rodent cells in culture. One open reading frame, designated STP-C488 (for saimiri-transformation-associated protein of the subgroup C strain 488), phenotypically transformed Rat-1 cells, resulting in formation of foci, growth at reduced serum concentration, and growth to higher cell densities. Cells transformed by STP-C488 formed invasive tumors in nude mice. The STP-A11 reading frame of strain 11 (subgroup A) was much less potent in its transforming ability than STP-C488. These results demonstrate the oncogene nature of these two open reading frames and provide a means for studying their transforming functions independent of the rest of the H. saimiri genome.