Transforming genes of retroviruses: definition, specificity, and relation to cellular DNA.

The oncogenic properties of sarcoma, acute leukemia, and lymphatic leukemia viruses are interpreted in terms of their genetic structures. Highly oncogenic sarcoma and acute leukemia viruses are shown to contain transforming onc genes which are different from the three virion genes (gag, pol, and env) essential for replication. Biochemical and genetic approaches to define onc genes are discussed. The hallmark of retroviral onc genes is shown to be a specific RNA sequence that is unrelated to essential virion genes. On this basis five different c1asses of onc genes can be distinguished in the avian tumor virus group alone: two of these, the onc genes of Rous sarcoma virus (RSV) and avian myeloblastosis virus (AMV) , share one design. Their coding sequence is a specific RNA section which either replaces env [RSV( -), AMV] or maps adjacent to the 3' end of env (RSV). Expression of this c1ass of onc genes is mediated via subgenomic mRNAs containing sequences from the 5' end of viral RNA spliced onto the onc gene coding sequences. The onc gene product of RSV has been identified as a 60,000-dalton phosphoprotein. Three other c1asses of onc genes, namely, those of the myelocytomatosis (MC29) subgroup of viruses, avian erythroblastosis virus (AEV), and Fujinami sarcoma virus (FSV), share another design. Their coding sequences are hybrids