The effect of canaline on some events in vaccinia virus replication

Canaline, a pyridoxal phosphate antagonist, is shown to inhibit two distinct events in the replication of vaccinia virus in HeLa cells. Initial events proceed in the presence of the inhibitor leading to the formation of DNA-containing, cytoplasmic inclusions. However, further DNA synthesis is required for the subsequent production of infectious progeny following the reversal of canaline inhibition by pyridoxal phosphate. Inhibition of a separate, maturation event is shown by the delayed addition of canaline resulting in the failure to coat virus-specific DNA synthesized previously in the absence of the inhibitor. Thus, the replication of vaccinia virus is sensitive to inhibition by canaline at an early and a late stage in the replication cycle. Reversal is accomplished alternatively by the addition of 'non-essential' amino acids suggesting that the effects of canaline result from inhibition of specific protein functions.