The specific inhibition of vesicular stomatitis virus replication by toyocamycin

Toyocamycin, an adenosine analog, inhibited the reproduction of vesicular stomatitis virus (VSV) by greater than 99%. The drug appeared to act preferentially at the level of replication since intracellular genome length 42 S RNA synthesis and the formation of viral nucleocapsids were inhibited by 90%, whereas VSV mRNA synthesis was reduced only by 50–60%. The VSV mRNAs were all polyadenylated in toyocamycin-treated cells, although the length of their poly(A) sequences increased slightly with increasing concentrations of the drug. Toyocamycin was incorporated into all intracellular VSV RNA species. In spite of the significant substitution of toyocamycin for adenosine into both the heteropolymeric and poly(A) regions of the VSV mRNAs, they were biologically functional since the viral L, G, N, NS, and M proteins were synthesized at about 20–40% of control values, levels approximately proportional to the amount of the mRNAs present.