Isolation of an MH2 retrovirus mutant temperature sensitive for macrophage but not fibroblast transformation.

A conditional mutant of the MH2 avian retrovirus, termed ts41MH2, was isolated. Unlike wtMH2, ts41MH2 permitted transformed macrophages to differentiate during a 5- to 7-day temperature shift from 37 to 42 degrees C. Mutant-infected cells incubated at 42 degrees C exhibited a flattened morphology and then fused to form giant multinucleated cells that closely resembled normal macrophage maturation in vitro. These differentiated cells reacted strongly with a myeloid-macrophage-specific monoclonal antibody. The process of differentiation was inhibited when ts41MH2-transformed nonproducer clones were superinfected before the temperature shift with the myc gene-containing MC29 or OK10 viruses. By contrast, no inhibition was observed in clones superinfected with the MH2-PA200 virus that contains only the mil gene. The mutant also demonstrated a reduced oncogenic potential relative to that of wtMH2 when it was inoculated intravenously into young birds. However, in contrast to the results obtained with hematopoietic cells, none of the five fibroblast transformation parameters tested for ts41MH2 were altered from those induced by wtMH2. These results suggest that the mutation in ts41MH2 is located in a region of myc required for macrophage transformation, but not required for fibroblast transformation.