Actinomycin D Acts on an Intracellular Process to Inhibit Replication of Rhinovirus Type 14

Abstract

Summary

Act D inhibited replication of RV14 but not mengovirus in HeLa cells. Early processes such as attachment, penetration, and uncoating of RV14 were not affected by Act D. Pretreatment of cells with Act D and removal of the antibiotic prior to infection increased the antiviral effect of Act D on replication of RV14. Yields of RV14 per cell were reduced in Act D-pretreated cell cultures but the number of virus-producing cells was not reduced. Cells treated with Act D for 6 hr prior to inoculation of RV14 synthesized only 28% of the ribonuclease-sensitive and ribonuclease-re-sistant RV14 RNA which was synthesized by cells treated with Act D at the time of virus inoculation. As most ribonuclease-re-sistant RNA is associated with viral replicative-intermediate RNA structures in these cells, the results are compatible with the hypothesis that a cell process is required for synthesis of viral replicative-intermediate RNA and it is the cell process with which Act D interferes and contributes to the reduction in RV14 yields.

I thank David R. L. LaBadie for conscientious and excellent technical assistance. This study was funded in part by an American Heart Association, Texas Affiliate, Inc. grant and by an Institutional Research grant from the University of Texas Health Science Center at San Antonio. I thank Kendall O. Smith and Stephen J. Mattingly for constructive criticisms of the manuscript.