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

The levels of two dsRNA-dependent enzyme activities, the pppA(2'p5'A)n synthetase (2-5A synthetase) and protein kinase were investigated in control and interferon-treated murine cells: L-929, K/Balb and NIH/3T3. Treatment of these cells with interferon resulted both in the establishment of the antiviral response and the development of anticellular effects. This latter was observed 3 days after treatment with interferon.

The levels of 2-5A synthetase and protein kinase in control and interferon-treated cells seemed to vary from one cell type to the other. In L-929 cells, both the 2-5A synthetase and protein kinase were induced by interferon as has been shown previously. On the other hand, treatment of NIH/3T3 cells with interferon resulted in the induction of 2-5A synthetase in the absence of any enhanced protein kinase activity. This lack of protein kinase in interferon-treated NIH/3T3 cells was not due to the presence of high levels of protein phosphatases. A third type of mouse cells, K/Balb cells, contained very high levels of 2-5A synthetase in the absence of any apparent resistance to virus infection. On treatment with interferon the level fo 2-5A synthetase in K/Balb cells remained constant while the protein kinase activity was enhanced by several fold. Both control and interferontreated K/Balb cells showed similar sensitivity to the action of exogenous 2-5A thus 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 action of interferon is discussed.