Papovaviruses as Probes to Study Developmental Changes in Embryonal Carcinoma Cells

Polyoma virus undergoes a productive infection, and SV40 expresses it’s early gene products in most differentiated mouse cells. On the other hand, neither virus is able to produce detectable levels of their early proteins in murine embryonal carcinoma cells (EC cells), which are the stem cells of teratocarcinomas (Swartzendruber and Lehman 1975; Boccara and Kelly 1978). If pluripotent EC cells are allowed to differentiate, these cells can then produce infectious polyoma virus or be transformed by SV40 and express early viral proteins (Topp et al. 1977; Maltzman et al. 1979). The block to polyoma or SV40 gene expression in murine EC cells has been investigated (Segal et al. 1979; Swartzendruber et al. 1977). Nullipotential F9 cells infected with SV40 have low levels of viral transcriptional intermediates and SV40 RNA. The viral RNA synthesized in F9 cells is not spliced into functional mRNA’s and thus early viral proteins are not expressed (Segal et al. 1979). Polyoma infection of pluripoent PCC-4-aza-1 EC cells results in extremly low levels of viral RNA compared to an infection of differentiated mouse cells (Katinka et al. 1980). Polyoma host range mutants have been isolated which produce infectious virus in PCC-4-aza-1 EC cells (Vasseur et al 1980), but fail to replicate in F9 EC cells. These data indicate that the block to papovavirus gene expression in EC cells may differ in two distinct EC cell lines (F9 and PCC-4-aza-1) and the expression of these early viral genes may be regulated by developmental changes in the cell type. As such, the papovaviruses appear to be excellent tools to probe the molecular basis of developmental regulation.