The acutely transforming avian retrovirus, MH2, carries a novel, putative oncogene, v-mil, in addition to the known oncogene, v-myc. We have recently shown by hybridization analysis that v-mil is homologous to v-raf, the transforming gene of the murine retrovirus, 3611-MSV. We have sequenced the v-mil oncogene and compared it with v-raf. The 80% homology between the nucleotide sequences and the 94% homology between the predicted amino acid sequences of the two viral genes clearly indicate that these are the avian and murine forms of the same gene. Comparison of the two sequences with that of the human cellular homolog indicates that v-raf has more 3' untranslated sequences, while v-mil has additional sequences from two 5' exons of the cellular homolog. Although the mil/raf amino acid sequences reveal partial homology to that of the v-src product, no tyrosine-specific protein kinase activity is detected for the gag-mil and gag-raf hybrid proteins. We have also determined the nucleotide sequence of MH2 from an HgiAI site within the coding region of its oncogene v-myc to the KpnI site within the long terminal repeat (LTR). Comparison with published sequences from other retroviruses allowed us to assign the origin of all sequence elements in this region. We conclude that MH2 contains a unique assembly of 3' terminal sequences which includes part of the 3' noncoding (SPC) region of the avian sarcoma virus, Y73, and the complete F3 and F1 segments of Rous sarcoma virus (RSV), strain SR-A. A unique MCF class of recombinant MuLV, associated with alveologenic lung carcinoma in mice was further characterized by sequencing its LTR. The results establish the unique structure of this new MCF class of viruses which has features of both the class I and class II MCF MuLV.
