Evidence for non-spliced SV40 RNA in undifferentiated murine teratocarcinoma stem cells

Abstract

UNDIFFERENTIATED murine teratocarcinoma stem cells do not support simian vacuolating virus 40 (SV40) or polyoma virus (Py) replication or even the expression of the early papovavirus proteins. These undifferentiated cells are also entirely refractory to infection with ecotropic murine C-type viruses. If the stem cells are allowed to differentiate to a variety of somatic cell types, they become susceptible to infection by SV40, Py and ecotopic murine C-type viruses1–4. In contrast, adenovirus type 2 can infect and replicate in the undifferentiated stem cells, although not as efficiently as it can in the differentiated mouse cells5 and certainly much less efficiently than it does in human cells. Studies on the mechanism of the resistance of the undifferentiated teratocarcinoma cells to infection by SV40 has shown that the block is not at the level of virus adsorption, penetration uncoating or transport to the nucleus6. We present here evidence indicating that the absence of expression of SV40 genetic information in nondifferentiated teratocarcinoma cells reflects an inability to generate stable viral mRNA. More specifically, the refractoriness of these cells to SV40 seems to be correlated, at least in part, with a deficiency in the splicing of viral mRNA.