Inhibition of vaccinia virus replication by canavanine and canaline.

Both L-canavanine, the oxyguanidinium analogue of arginine, and L-canaline, the equivalent oxyamine analogue of ornithine, inhibit the replication of vaccinia virus in HeLa cells. Inhibition by canavanine is reversed progressively by the simultaneous addition of increasing amounts of arginine but inhibition by canaline is not reversed by addition of ornithine. However, the inhibitory effect of canaline is reversed progressively by the simultaneous addition of increasing amounts of pyridoxal phosphate. The effect of canavanine on virus production is suppressed completely by the presence of a tenfold greater concentration of arginine: the effect of canaline is suppressed completely by the presence of an equimolar concentration of pyridoxal phosphate. Additionally, the inhibition of virus growth in canalinetreated cells is reversed partially by the subsequent addition of pyridoxal phosphate. These observations suggest that canavanine inhibits competitively as a result of its structural analogy to arginine but that canaline does not act as a structural analogue of ornithine. It is proposed that canaline inhibits by its interaction with pyridoxal phosphate which results in a deficiency of this cofactor. The effect of each inhibitor on the incorporation of precursors of DNA, RNA and protein into both infected and control cells is reported. These results are compatible with the mode of action proposed for each inhibitor.