title: Mechanism of Mengo virus-induced cell injury in L cells: use of inhibitors of protein synthesis to dissociate virus-specific events.
abstract: L cells were infected with Mengo virus in the presence of varying concentrations of protein synthesis inhibitors (azetidine-2-carboxylic acid, p-fluorophenylalanine, puromycin), and examined with respect to the effects of the inhibitors on several features of virus-induced cell injury. The virus-specific events in the cells could be dissociated into three groups, based on their sensitivity to the inhibitors: (i) viral ribonucleic acid (RNA) synthesis, bulk viral protein synthesis, and infectious particle production, all of which were prevented by low inhibitor concentrations; (ii) the cytopathic effect (CPE) and stimulation of phosphatidylcholine synthesis, which were sensitive to intermediate concentrations of the inhibitors; and (iii) the virus-induced inhibitions of host RNA and protein synthesis, which were resistart to the inhibitors of protein synthesis except at very high concentrations. It is concluded from this that the virus-induced CPE and stimulation of phosphatidylcholine synthesis are not consequences of the inhibition of cellular RNA or protein synthesis. Analysis of the virus-specific protein and RNA synthesized at several concentrations of azetidine and puromycin suggests that the CPE may be induced by a viral protein precursor. Virus-induced inhibition of host RNA and protein synthesis occurred at azetidine concentrations which blocked the synthesis of over 99.7% of the total viral RNA and over 99% of the viral double-stranded RNA (dsRNA). Calculations show that this would correspond to less than 150 dsRNA molecules per infected cell, resulting in a dsRNA-polysome ratio of less than 1:1,000; this indicates that host protein synthesis cannot be inhibited by an irreversible binding of dsRNA to polysomes.
mesh_terms: D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology*; D002247:Carbon Isotopes; D002794:Choline / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006801:Humans; D007739:L Cells / Q000187:drug effects / Q000382:microbiology*; D008574:Mengovirus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D010452:Peptide Biosynthesis; D010713:Phosphatidylcholines / Q000096:biosynthesis; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D011691:Puromycin / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis; D014316:Tritium; D014529:Uridine / Q000378:metabolism; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000596:Amino Acids; D002247:Carbon Isotopes; D010713:Phosphatidylcholines; D012367:RNA, Viral; D014764:Viral Proteins; D014316:Tritium; D011691:Puromycin; D012313:RNA; D002794:Choline; D014529:Uridine