Mechanism of interferon action: inhibition of vesicular stomatitis virus replication in human amnion U cells by cloned human leukocyte interferon. II. Effect on viral macromolecular synthesis.
The effects of a single molecularly cloned subspecies of human leukocyte interferon (IFN-alpha A) on vesicular stomatitis virus (VSV) macromolecular synthesis in human amnion U cells were examined. IFN-alpha A was found to uniformly inhibit VSV protein synthesis to an extent sufficient to account for the overall inhibition of viral infectivity. IFN-alpha A treatment also prevented the shutoff of cellular protein synthesis observed in untreated, VSV-infected U cells. By use of the VSV mutant tsG41, which is competent in RNA transcription but defective in RNA replication at 40 degrees C, it was shown that IFN did not significantly inhibit the accumulation of VSV primary transcripts, although the in vivo translation of primary viral transcripts was greatly impaired as a function of IFN treatment. Thus, the major, and possibly only, effect of IFN-alpha A on VSV replication was translation inhibition. Analysis of RNA, separated by agarose gel electrophoresis after denaturation with glyoxal, with cDNA probes to individual VSV mRNAs, did not reveal any detectable difference in the structural integrity of VSV mRNA isolated from IFN-treated as compared to untreated cells. Likewise, in vitro protein synthesis did not reveal any major difference in the functional integrity of VSV mRNA isolated from IFN-treated as compared to untreated U cells. Viral mRNA isolated from either wild type or tsG41-infected U cells treated with IFN was translated only slightly less efficiently in vitro than viral mRNA from untreated cells. Thus, the principal cause of the IFN-induced inhibition of viral protein synthesis observed in vivo appears to be an alteration of a component of the translational machinery other than the mRNA template.
D000650:Amnion / Q000378:metabolism*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D005796:Genes / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007700:Kinetics; D011247:Pregnancy; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
D007370:Interferon Type I; D012333:RNA, Messenger; D014764:Viral Proteins