Effects of the Copper Chelators Diethyldithiocarbamate and Bathocuproine Sulfonate on Interferon and Its Antiviral State

Treatment of mouse L cells with two structurally unrelated chelators of copper ions, diethyldithiocarbamate (DDC) or bathocuproine sulfonate (BCS), completely inhibited the ability of interferon (IFN) to inhibit mengovirus growth. However, mengovirus virions were inactivated by incubation with DDC, and DDC induced a generalized inhibition of cellular RNA and protein synthesis, possibly combined with the inactivation of one or more specific enzymatic activities involved in the establishment or maintenance of the antiviral state. In contrast, BCS had no effect on either cell or virus growth. BCS combined with trace copper ions in the growth medium and the resulting complex prevented IFN from interacting properly with cellular receptors, apparently by binding noncovalently to the IFN molecules. In some cases, IFN was irreversibly inactivated, probably due to oxidation of essential cystein, tyrosine, or tryptophan residues by the (BCS)₂Cu²⁺ complex. BCS was at least as effective as anti-IFN antibody at neutralizing cell-bound IFN, and has a number of advantages over it.