[Mechanism of virus-induced leukemogenesis in an animal model system]

Retroviruses can cause different types of leukemias in chickens. A small group of virus strains induce acute leukemias and transform hematopoietic cells in vitro. We have shown that cells transformed in vitro by erythroblastosis and myeloblastosis viruses resemble in vivo transformed cells in their phenotype of differentiation. The erythroblastosis virus AEV carries two cell-derived oncogenes termed erbA and erbB. The analysis of AEV using deletion mutants showed that erbB is the main oncogene which is capable of inducing a "mild" form of erythroleukemia. The added action of the erbA oncogene leads to an aggressive, more "advanced" form of erythroleukemia. The erbA oncogene itself, however, does not exhibit any detectable biological activity. Using temperature sensitive mutants of AEF we could also show that erbB, together with erbA, blocks the differentiation of hematopoietic precursor cells. The continued synthesis of a functional erbB-encoded protein is necessary to maintain the "blocked", i.e. leukemic state of the infected cells.