Polyoma DNA sequences involved in control of viral gene expression in murine embryonal carcinoma cells

Polyoma virus can develop lytically in differentiated mouse cells, but is unable to express either early or late functions in undifferentiated early embryonic cells or in embryonal carcinoma (EC) cells of the mouse. However, the EC cells become susceptible during differentiation and then behave as do mouse somatic cells. We have recently described the isolation of a new class of polyoma virus mutant (Py EC) able to develop normally in an EC cell line (PCC4-Aza) that is capable of trigerminal differentiation in vivo but exhibits a very limited differentiation in vitro. The mutants do not grow in another EC cell line (F9) that is 'blocked'--'nullipotent' in vivo, but able to differentiate in vitro when grown in the presence of chemical inducers. Compared with their parental strain, all Py EC genomes analysed so far have an extra 20-50 bases in their HpaII-3 restriction fragment. We now describe polyoma mutants that will grow in EC F9 cells, and the sequence changes in two of them. The region involved in the mutations can be folded into a putative tRNA-like secondary structure which may be involved in the regulation of viral early transcription with respect to the state of differentiation of the host cell.