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

Abstract

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 classes 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 class 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 classes 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 consisting of specific as well as of gag or gag and pol gene-related elements. The products of these onc genes, translated from full size genomic RNA, are hybrid proteins carrying gag or gag and pol determinants in addition to specific sequences. They are phosphorylated and range in size from 75,000 to 200,000 daltons. Since viruses with totally different onc genes can cause the same disease (namely, RSV, FSV, AEV, and MC29 cause sarcoma and AEV, AMV, or E26 and MC29 cause erythroblastosis), it is concluded that multiple mechanisms involving multiple cellular targets exist for sarcomagenic and leukemic transformation of the avian cell. Comparisons between viral onc genes of the RSV-design and in particular those of the hybrid design and one-related chromosomal DNA sequences of the cell suggest qualitative differences. Hence viral onc genes are not simply transduced cellular genes, and cellular sequences related to viral onc genes appear not directly relevant to cancer. It follows that viral onc genes are unique and more than the sum of their parts related to cellular DNA and to replicative genes of retroviruses. We speculate that onc genes also may plan a role indirectly in cancers caused by lymphatic leukemia viruses, although these viruses are not known to contain such genes.KeywordsRous Sarcoma VirusHelper VirusAvian Leukosis VirusAvian Sarcoma VirusMurine Sarcoma VirusThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.