Application of Manometric Method to Testing Chemical Agents in vitro for Interference with Poliomyelitis Virus Synthesis. †

Summary

DL-ethionine, 2,6-diaminopurine, benzimidazole, and β-2-thienylalanine did not inhibit the synthesis of poliomyelitis virus, Type 1, in strain HeLa cell cultures except at concentrations which were markedly inhibitory to the respiration of the host cell. Cessation of respiration of infected cultures occurred at the same time independent of the concentration of the metabolic analogue employed or of the final concentration of virus. The ethionine-induced inhibition of respiration was only partially reversed by the addition of methionine. A concentration of benzimidazole, 0.25 mg/ml, which was not toxic for HeLa cells, as assessed by microscopic observations, was markedly inhibitory to the respiration of cells in a Warburg flask. The importance of the oxidative energy of respiration for the synthesis of poliomyelitis virus, Type 1, by HeLa cells was demonstrated. Anaerobically, such cells were able to produce less than 0.01% of the amount of virus produced by replicate systems under aerobic conditions. The advantages of a homogeneous cell culture over mixed cell cultures for studies of chemical inhibition of virus synthesis are discussed. Cellular uniformity permits precise allocation of the observed effects of a test agent to cells capable of propagating the virus.