Mechanism of interferon-induced inhibition of early simian virus 40 (SV40) functions

Abstract

The mechanism of interferon-induced inhibition of early simian virus 40 (SV40) functions was studied in both permissive and nonpermissive cells. The following observations indicate that the step in SV40 replication which is sensitive to the action of interferon is located at a very early stage of infection and suggest that SV40-DNA in the infecting virions cannot be converted to a functional form for transcription by the action of interferon. 1) Synthesis of early viral mRNA as well as T antigen was completely inhibited by interferon when monkey cells were infected at a relatively low multiplicity. This inhibition, however, could be partially overcome by infecting the cells at a high multiplicity. Similar multiplicity-dependent leakiness of the interferon-induced inhibition of viral early functions was observed in nonpermissive mouse cells. 2) Inhibition of SV40-DNA synthesis by interferon was not complemented by the early gene products present in SV40-transformed monkey cells (clone T22). SV40-DNA of the infecting virions was unable to replicate in T22 cells pretreated with interferon. 3) The synthesis of SV40-DNA and -mRNA and the formation of T and V antigens were much less inhibited by interferon when monkey cells were infected with the infectious DNA. The 20–50% decrease in synthesis of these macromolecules seems to be caused by relatively inefficient penetration of DNA to the nuclei of interferon-treated cells. Under the same conditions, synthesis of these macromolecules was completely inhibited by interferon in the virion-infected cells.