title: Abnormal behavior of interferon-induced enzymatic activities in an interferon-resistant cell line.
abstract: Interferon induces two double-stranded RNA-dependent enzymatic activities: an oligoisoadenylate synthetase that converts ATP to ppp(A2'p)n5'A, and a protein phosphokinase. We have explored the level and inducibility of these two enzymes in a human cell line (HEC-1) totally insensitive to both the antiviral and the anticellular actions of interferon. The activities of both enzymes are high in untreated cells and only minor changes occur after treatment with interferon, even at high concentrations. Interferon-treated HEC-1 cells do not contain an inhibitor of the oligoisoadenylate synthetase activity. The products of this HEC-1 oligoisoadenylate synthetase consist mainly of dimers, trimers, and tetramers as found in other cell lines after interferon treatment. The synthetase level is unaffected by treating the cells with anti-interferon antiserum, indicating that the results cannot be explained by a spontaneous low production of interferon by these cells. Furthermore, virus multiplication is not inhibited, even after treatment with interferon. These observations suggest that either the two enzymatic activities do not suffice for the establishment of an antiviral state in vivo or that a regulatory control mechanism, lost in these cells and common for both enzymes, is required for the expression of the antiviral action of interferon. This might explain both the constitutivity of the two enzymes and the interferon resistance observed.
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase; D002460:Cell Line; D004351:Drug Resistance; D004720:Endonucleases / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D011118:Polynucleotide Ligases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D007372:Interferons; D011494:Protein Kinases; D015088:2',5'-Oligoadenylate Synthetase; D004720:Endonucleases; D011118:Polynucleotide Ligases