Lack of Systematic Correlation between the Interferon Mediated Antiviral State and the Levels of 2-5A Synthetase and Protein Kinase in Three Different Types of Murine Cells

Abstract
The levels of 2 ds[double-stranded]RNA-dependent enzyme activities, pppA(2''p5''A)n synthetase (2-5A synthetase) and protein kinase, were investigated in control and interferon[IFN]-treated murine cells: L-929, K/Balb and NIH/3T3. Treatment of these cells with IFN resulted in the establishment of the antiviral response and the development of anticellular effects. The latter effect was observed 3 days after IFN treatment. The levels of 2-5A synthetase and protein kinase in control and interferon-treated cells seemed to vary among cell types. In L929 cells, both the 2-5A synthetase and protein kinase were induced by IFN. Treatment of NIH/3T3 cells with IFN resulted in the induction of 2-5A synthetase in the absence of any enhanced protein kinase activity. This lack of protein kinase in IFN-treated NIH/3T3 cells was not due to the presence of high levels of protein phosphatases. K/Balb cells contained very high levels of 2-5A synthetase in the absence of any apparent resistance to virus infection. On treatment with IFN, the level of 2-5A synthetase in K/Balb cells remained constant while the protein kinase activity was enhanced severalfold. Control and IFN-treated K/Balb cells showed similar sensitivity to the action of exogenous 2-5A, suggesting that the 2-5A system (the 2-5A dependent nuclease and the phosphodiesterase which degrades 2-5A) was not altered on treatment with interferon. The significance of these results in relation to the mechanism of the antiviral action of IFN is discussed.