Mechanism of interferon action: further evidence for transcription as a primary site of action in simian virus 40 infection

Interferon inhibits the replication of simian virus 4o (SV4o) in monkey cells and reduces markedly the formation of both early virus protein (i.e. SV4o T antigen) and early SV4o RNA. This suggests that in SV4o infection interferon acts pri-marily by inhibiting transcription. To test this conclusion further, we examined alternative mechanisms which might explain these results and made the following observations. (I) The quantity of input SV4o DNA in the nucleus 24 h post infection (p.i.) was the same in interferon-treated and control cells. Thus interferon does not appear to diminish the quantity of SV4o DNA template available for transcription. (2) Chemical inhibitors of protein synthesis did not mimic the selective inhibition of early SV4o RNA formation induced by interferon, indicating that the transcription of early SV4o RNA is not dependent upon the prior synthesis of any virus-induced protein. Thus a block in translation cannot readily explain the reduced formation of early SV4o RNA in interferon-treated cells. (3) Fractionation of SV4 o infected cells after a one-hour labelling period showed that interferon produced a comparable r duction in the quantity of early SV4o RNA in the nucleus and the cytoplasm. Thus the observed inhibition of early SV4o RNA is not due solely (if at all) to enhanced cytoplasmic degradation. These results indicate that the primary effect of interferon in SV4o infected monkey cells is either to inhibit the transcription of early virus RNA or to enhance its turnover in the nucleus