INHIBITION OP MULTIPLICATION 219 



metabolic activities of the virus-infected cell, it would be surprising if such 

 results had not been secured. 



The multiplication of influenza viruses in the chorioallantoic membrane 

 in vitro requires oxygen (Ackermann, 1951b; Tamm, 1956b). Pentamidine 

 (Eaton et al., 1952), 2, 5-dimethylbenzimidazole (Tamm et al., 1953a) and 

 antimycin A (Ackermann and Francis, 1954), at concentrations which 

 diminish the oxygen uptake of the membrane, inhibit the multiplication of 

 influenza viruses. It appears that the inhibitory effect is secured only if the 

 endogenous respiration of the membrane is diminished during the latent 

 period. 



DL-Ethionine, 2, 6-diaminopurine, benzimidazole and /3-2-thienylalanine, 

 at concentrations which markedly inhibit the respiration of HeLa cells in 

 vitro, also inhibit the multiplication of poliovirus, type 1 (Gifford et al., 1954). 

 At lower concentrations which do not diminish oxygen uptake, these 

 compounds have no inhibitory activity against this virus. 



The synthesis of influenza virus appears to be dependent upon some 

 oxidative reactions of the Krebs cycle (Ackermann, 1951b). Chemical 

 inhibition of enzymes of the citric acid cycle by malonate or fluoroacetate 

 inhibited influenza virus multiplication. Such inhibition was demonstrated 

 in the lungs of mice (Ackermann, 1951c). Later work showed that fluoro- 

 acetate delayed but did not prevent the multiplication of influenza virus or 

 pneumonia virus of mice in the mouse lung or influenza and mumps viruses in 

 the allantoic sac (Mogabgab and Horsfall, 1952). 



2, 4-Dinitrophenol stimulates tissue respiration but inhibits oxidative 

 phosphorylation. The compound inhibits the multiplication of influenza 

 virus in the chorioallantoic membrane in vitro (Eaton, 1952; Ackermann and 

 Johnson, 1953); the degree of inhibition is correlated with the extent of 

 stimulation of respiration and release of phosphate. It has been suggested that 

 the energy required for virus synthesis derives from the oxidative phosphory- 

 lative activity of the host tissue. 



VI. Modification op Cell Damage 



The virus-infected cell is metabolically different from the uninfected host 

 cell. Recent evidence bearing on the metabolic alterations have been 

 summarized by Tamm (1958) and new data have appeared since (Boyer et al., 

 1957; Maassab et al., 1957; Levy et al., 1957). In the majority of instances, the 

 multiplication of animal viruses leads to the production of definite abnor- 

 malities in infected host cells. Whether the damage that occurs in the virus- 

 infected cell results from the biosynthetic alterations that are required for the 

 process of multiplication or from the products of the process is not yet clear 

 (Horsfall and Tamm, 1957). 



