Abstract
It has been demonstrated that a saturating dose of diphtheria toxin produced a 90% inhibition of polio-virus replication in HeLa cells. This inhibition was reflected in infectious viral RNA synthesis and in mature virus production. Toxin had no direct effect on virus particles or I-RNA, and poliovirus adsorption and eclipse appeared to be carried out normally in intoxicated cells. When toxin was given at various time intervals after infection, the amount of inhibition depended on the time of toxin addition. Toxin given before or immediately after infection gave maximum inhibition, while toxin given several hours after infection had little effect. The data suggest that toxin inhibits viral replication through its effect on protein synthesis. It is likely that a critical step in the viral replication cycle, the production of poliovirus-induced RNA polymerase, is inhibited, and possibly the synthesis of capsid protein. Ammonium salts and the aliphatic amines, glycamine and prolamine, prevented the inhibition of viral replication by toxin. The kinetics of the protective action of ammonium chloride and diphtheria antitoxin are remarkably similar.
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Selected References
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- BALTIMORE D., EGGERS H. J., FRANKLIN R. M., TAMM I. Poliovirus-induced RNA polymerase and the effects of virus-specific inhibitors on its production. Proc Natl Acad Sci U S A. 1963 Jun;49:843–849. doi: 10.1073/pnas.49.6.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BALTIMORE D. IN VITRO SYNTHESIS OF VIRAL RNA BY THE POLIOVIRUS RNA POLYMERASE. Proc Natl Acad Sci U S A. 1964 Mar;51:450–456. doi: 10.1073/pnas.51.3.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- COLLIER R. J., PAPPENHEIMER A. M., Jr STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN. II. EFFECT OF TOXIN ON AMINO ACID INCORPORATION IN CELL-FREE SYSTEMS. J Exp Med. 1964 Dec 1;120:1019–1039. doi: 10.1084/jem.120.6.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DARNELL J. E., Jr, LEVINTOW L., THOREN M. M., HOOPER J. L. The time course of synthesis of poliovirus RNA. Virology. 1961 Mar;13:271–279. doi: 10.1016/0042-6822(61)90145-3. [DOI] [PubMed] [Google Scholar]
- GIERER A., SCHRAMM G. Infectivity of ribonucleic acid from tobacco mosaic virus. Nature. 1956 Apr 14;177(4511):702–703. doi: 10.1038/177702a0. [DOI] [PubMed] [Google Scholar]
- HOLLAND J. J., HOYER B. H. Early stages of enterovirus infection. Cold Spring Harb Symp Quant Biol. 1962;27:101–112. doi: 10.1101/sqb.1962.027.001.013. [DOI] [PubMed] [Google Scholar]
- HOLLAND J. J., HOYER B. H., McLAREN L. C., SYVERTON J. T. Enteroviral ribonucleic acid. I. Recovery from virus and assimilation by cells. J Exp Med. 1960 Nov 1;112:821–839. doi: 10.1084/jem.112.5.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HOLLAND J. J. Irreversible eclipse of poliovirus by HeLa cells. Virology. 1962 Feb;16:163–176. doi: 10.1016/0042-6822(62)90292-1. [DOI] [PubMed] [Google Scholar]
- HOLLAND J. J., McLAREN L. C. Improved method for staining cell monolayers for virus plaque counts. J Bacteriol. 1959 Oct;78:596–597. doi: 10.1128/jb.78.4.596-597.1959. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KATO I., PAPPENHEIMER A. M., Jr An early effect of diphtheria toxin on the metabolism of mammalian cells growing in culture. J Exp Med. 1960 Aug 1;112:329–349. doi: 10.1084/jem.112.2.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim K., Groman N. B. In vitro inhibition of diphtheria toxin action by ammonium salts and amines. J Bacteriol. 1965 Dec;90(6):1552–1556. doi: 10.1128/jb.90.6.1552-1556.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LENNOX E. S., KAPLAN A. S. Action of diphtheria toxin on cells cultivated in vitro. Proc Soc Exp Biol Med. 1957 Aug-Sep;95(4):700–702. doi: 10.3181/00379727-95-23335. [DOI] [PubMed] [Google Scholar]
- PLACIDO SOUSA C., EVANS D. G. The action of diphtheria toxin on tissue cultures and its neutralization by antitoxin. Br J Exp Pathol. 1957 Dec;38(6):644–649. [PMC free article] [PubMed] [Google Scholar]
- STRAUSS N., HENDEE E. D. The effect of diphtheria toxin on the metabolism of HeLa cells. J Exp Med. 1959 Feb 1;109(2):145–163. doi: 10.1084/jem.109.2.145. [DOI] [PMC free article] [PubMed] [Google Scholar]