Differentiation as a requirement for simian virus 40 gene expression in F-9 embryonal carcinoma cells.

Abstract

Infection of differentiated mouse embryo cells by SV-40 leads to the production of the early mRNA and the tumor (T) antigens that they encode. In contrast, undifferentiated F-9 murine teratocarcinoma cells do not support these early stages of the SV-40 cycle. This block results from the inability to accumulate stable processed early SV-40 mRNA. Vitamin A and its derivatives can induce in vitro differentiation of stem cells. Undifferentiated F-9 cells, upon treatment with a low concentration of retinoic acid, exhibited pronounced morphologic changes and the appearance of the H-2 surface antigens. After differentiation, the susceptibility of F9 cells to SV-40 infection could be demonstrated by the appearance of large T and small T antigens, as shown by immunoflorescence and immunoprecipitation. S1 nuclease mapping of early SV-40 transcripts confirmed the presence of the 2 spliced early mRNA. The undifferentiated F-9 stem cells contain the genetic information needed for generating stable processed early SV-40 mRNA, but are blocked in the production of functional species.