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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.

Oncogenes have been intimately associated with the genesis of human neoplasms. A particularly useful system to study the mechanism of tumorigenesis is a small group of avian retroviruses that carry two oncogenes. These viruses causes acute leukemias and can transform hematopoietic cells in vitro. The mechanisms by which viral oncogenes affect the growth control and differentiation of their target cells is now understood in fair detail for two of these virus strains. In the avian erythroblastosis virus AEV, the v-erbB oncogene deregulates the growth control of erythroid precursors, while verbA blocks their terminal differentiation into erythrocytes. Based on the findings that v-erbB oncogene corresponds to a mutated growth factor receptor gene and that v-erbA corresponds to a mutated hormone receptor gene, models have been developed that explain the function of these two oncogenes on a molecular basis. The myelomonocytic leukemia virus MH2 acts by a completely different mechanism. In this case, the v-myc oncogene stimulates the proliferation of macrophage-like cells, while the v-mil gene stimulates them to produce their own growth factor, thus leading to autocrine growth. It will be interesting to determine whether the type of mechanisms of oncogene cooperativity elucidated for acute leukemia viruses are also operative during leukemogenesis in humans.