Mutagenesis of the v-mht/mil oncogene in avian carcinoma virus MH2

Avian carcinoma retrovirus MH2 induces leukemia and solid tumors in chickens and transforms fibroblasts and macrophages in vitro. The genome of MH2 consists of two oncogenes, v-mht/mil and v-myc. Most of the transforming activity of MH2 is attributed to the v-myc oncogene. In contrast, the v-mht/mil oncogene alone does not induce a fully transformed phenotype of avian primary fibroblasts in vitro. It was shown previously that v-mht/mil is the avian homology of the v-raf oncogene in murine sarcoma retrovirus 3611. Because the v-raf oncogene transforms murine fibroblasts very efficiently, the present study tested the hypothesis that an extra segment in the 5' end of v-mht/mil relative to v-raf suppressed the fibroblast-transforming activity of v-mht/mil. By introducing an in-frame deletion of 195 nucleotides into the 5' end of v-mht/mil, the results demonstrate that in the presence of an inactive v-myc oncogene, the 5'-deleted v-mht/mil oncogene fails to transform chicken embryo fibroblasts. Therefore, it is likely that avian primary fibroblasts lack a cellular component that serves as a critical substrate/target for v-mht/mil-induced cellular transformation.