Temperature‐sensitive mutants of MH2 avian leukemia virus that map in the v‐mil and the v‐myc oncogene respectively.

MH2 is an avian retrovirus that contains the v‐mil and v‐myc oncogenes. In vitro it transforms chick macrophages that are capable of proliferation in the absence of growth factor. Earlier work showed that v‐myc induces macrophage transformation and that v‐mil induces the production of chicken myelomonocytic growth factor (cMGF), thus generating an autocrine system. We describe the isolation of temperature‐sensitive (ts) mutants of MH2 virus. As suggested by marker rescue experiments, one mutant bears a ts lesion in v‐mil, whereas the other carries a mutation in v‐myc. Ts v‐mil MH2‐transformed macrophages become factor‐dependent at the non‐permissive temperature (42 degrees C), while ts‐v‐myc MH2‐transformed macrophages cease growing and acquire a more normal macrophage phenotype at 42 degrees C irrespective of the presence of cMGF. Both phenotypes can be reversed by backshift to the permissive temperature. These results suggest that the gene products of v‐mil and v‐myc function independently of each other and that v‐mil is necessary for the maintenance of autocrine growth, whereas v‐myc is required to maintain the transformed phenotype.