Inhibition of protein synthesis in reovirus-infected HeLa cells with elevated levels of interferon-induced protein kinase activity.
Protein synthesis was inhibited in one line of interferon-treated HeLa cells (line 2) upon infection with reovirus, but not in different HeLa cells (line 1) treated in the same way. The inhibition resulted in polysome runoff, suggesting that it was due to an impairment of peptide chain initiation. Interferon induces the synthesis of a protein kinase, which is activated in cell-free systems by double-stranded RNA and phosphorylates the alpha subunit of eukaryotic initiation factor 2, thus inhibiting the initiation of protein synthesis. Therefore, we measured the level of this protein kinase in extracts prepared from the two HeLa cell lines. Cells of line 2 showed about 3-4 times more protein kinase activity than cells of line 1. The inhibition of protein synthesis upon infection with reovirus was correlated with an increased phosphorylation of the alpha subunit of eukaryotic initiation factor 2 in interferon-treated cells labeled with 32P. The kinase was presumably activated in intact cells by viral double-stranded RNA, but this activation resulted in inhibition of protein synthesis only in cells with elevated levels of the kinase.
D002472:Cell Transformation, Viral; D015852:Eukaryotic Initiation Factor-2; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D007700:Kinetics; D009363:Neoplasm Proteins / Q000235:genetics*; D010448:Peptide Initiation Factors / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics*; D011506:Proteins / Q000378:metabolism; D012087:Reoviridae / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism
D015852:Eukaryotic Initiation Factor-2; D009363:Neoplasm Proteins; D010448:Peptide Initiation Factors; D011506:Proteins; D007372:Interferons; D011494:Protein Kinases; D011070:Poly I-C