Selective inhibition of viral gene expression as the mechanism of the antiviral action of PGA1 in vaccinia virus-infected cells.
We have previously shown that prostaglandins of the A series are potent inhibitors of the replication of several animal viruses in cultured cells. In this report we have studied the mechanism of the antiviral action of PGA1 in vaccinia virus-infected mouse L cells, where there is an alteration in both the rate and extent of the synthesis of some virus proteins. When cytoplasmic RNAs from PGA-treated, vaccinia virus-infected cells were translated in cell-free systems, similar selective inhibition of the synthesis of some viral polypeptides was observed. The lack of translation of some viral RNAs was not due to an impairment of the methylation process nor to a difference in ionic requirements. PGA1, even at doses as high as 10 micrograms/ml, did not exert any direct inhibitory action on transcription in vitro as measured in two cell-free systems, and had no effect on primary transcription-translation of vaccinia virus RNAs when assayed in coupled cell-free systems. Southern blot hybridization analysis of cytoplasmic RNAs to EcoRI restriction fragments of vaccinia DNA showed that PGA1 was able to induce major changes in the pattern of RNA transcripts during the course of viral infection. We propose that changes in the transcription programme of vaccinia virus RNAs could be due either to an alteration of specific viral proteins that regulate transcription by direct binding of PGA1, or to the synthesis and/or activation of a host product that mediates the antiviral action.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005814:Genes, Viral; D066298:In Vitro Techniques; D051379:Mice; D011454:Prostaglandins A / Q000494:pharmacology*; D012367:RNA, Viral / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects; D014616:Vaccinia virus / Q000187:drug effects / Q000235:genetics*; D014764:Viral Proteins / Q000096:biosynthesis
D000998:Antiviral Agents; D011454:Prostaglandins A; D012367:RNA, Viral; D014764:Viral Proteins; C100573:prostaglandin A1