Selective inhibition of protein synthesis in virus-infected mammalian cells.
A number of translation inhibitors were tested for their effects on both control and encephalomyocarditis virus-infected mouse 3T6 cells. The virus-infected cells were specifically inhibited by gougerotin, edeine, and blasticidin S, whereas these drugs failed to penetrate into uninfected cells. Inhibition of infected cells by gougerotin became apparent when the synthesis of viral proteins commenced, suggesting that the latter process is accompanied by a permeability change in the cells that allows uptake of the drug. This permeability change was not observed in cells treated with cycloheximide soon after viral infection, although treatment with actinomycin D did not prevent inhibition of gougerotin. It is possible, therefore, that a specific viral protein is involved in the permeability change of the plasma membrane. Moreover, gougerotin was unable to inhibit protein synthesis in the presence of zinc ions, thus preventing gougerotin from entering into the infected cell. Membrane leakiness was not restricted to the encephalomyocarditis virus-3T6 system; it was also observed in mengovirus-infected 3T6 cells, Semliki Forest virus-infected BHK cells, and simian virus 40-infected CVI1 cells at the time in which the synthesis of late proteins is maximal.
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002460:Cell Line; D002463:Cell Membrane Permeability; D004486:Edeine / Q000494:pharmacology; D004686:Encephalomyocarditis virus / Q000254:growth & development*; D006146:Guanidines / Q000494:pharmacology; D008574:Mengovirus / Q000254:growth & development*; D014176:Protein Biosynthesis / Q000187:drug effects; D011741:Pyrimidine Nucleosides / Q000494:pharmacology; D012672:Semliki forest virus / Q000254:growth & development*; D013539:Simian virus 40 / Q000254:growth & development*; D014764:Viral Proteins / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D006146:Guanidines; D011741:Pyrimidine Nucleosides; D014764:Viral Proteins; D004486:Edeine; C004942:gougerotin