A. Prinzie

Mechanism of action of interferon

Several workers have described the inhibition of virus growth within infected cells treated with interferon. It has been shown that interferon has no effect on extracellular virus and that it does not affect virus absorption into the host cell. These results suggest that the mechanism of action of interferon is intracellular. ISAACS et al. (1961) have shown biochemical and biological similarities of behavior between interferon and known substances which uncouple oxidative phosphorylation. These authors think that this might represent the mechanism through which interferon inhibits virus synthesis in the cell. Several findings support their hypothesis. In the course of our investigations about interferon influence on isolated polio RNA, using either tissue culture system or embryonated eggs, we have observed that mixing in vitro of polio RNA and interferon or simultaneous inoculation of both compounds results in a complete inhibition of viral synthesis. It has been shown that infection of the embryonated egg with polio RNA results in a one cycle multiplication of virus. From these observations, we have developed the hypothesis that interferon might act by a direct interaction with infecting viral RNA. We have also studied this phenomenon in cells infected with WEE virus. When infectious RNA is extracted from cells at early periods after infection, it is possible to demonstrate with this virus the presence of a precursor RNA or of true viral I~NA, depending on the temperature of extraction. With this method, we have shown that interferon action was already demonstrable at the time when only precursor RNA is present in the cell. This would suggest that blocking of RNA formation by