Analysis of the transforming functions of bovine papillomavirus type 4

Bovine papillomavirus type 4 (BPV-4) morphologically transforms primary bovine cells in vitro only in the presence of an activated ras gene. The transformed cells are capable of anchorage-independent growth, but are not immortal and are incapable of inducing tumors in nude mice. BPV-4 does not possess an E6 ORF and failure to induce full transformation may be due to the lack of this gene. Here we report the contribution of individual BPV-4 genes to cell transformation and the effect of adding the E6 ORF of HPV-16 to the system. We show that BPV-4 E7 ORF is responsible for morphological transformation, the E8 ORF is responsible for anchorage-independent growth, and addition of HPV-16 E6 ORF rescues cells from senescence. By immunocytostaining, E7 and E8 have been visualized in transiently transfected cultured cells. E8 is localized in the membranes while E7 is found both in the cytoplasm and in the nucleus.