GROWTH, DEVELOPMENT, AND DIFFERENTIATION 



193 



with influenza type A virus isolated from man and cultured in chick chorio- 

 allantoic membrane illustrate this well. Ackermann (1951) found that mal- 

 onate inhibits the formation of virus and simultaneously reduces the oxygen 

 uptake of the host cells (see accompanying tabulation). Malonate is not 



virucidal since the original virus can be recovered from the infected cul- 

 tures. The major effect of malonate is not to prevent infection of the cells, 

 since essentially the same results were obtained when malonate was added 

 4 hr after the inoculation of the virus. The inhibition is thus exerted on 

 the synthesis of new virus material. Furthermore, the host cells are not 

 damaged; if infected chorioallantoic tissue is exposed to 60 mM malonate 

 for 24 hr, virus proliferation is completely inhibited but, if the tissue is 

 washed free of malonate, becomes susceptible to infection and supports 

 virus multiplication. These results were confirmed and extended by Eaton 

 (1952), who reported that 42 niM malonate completely inhibits virus mul- 

 tiplication, inhibits respiration around 50%, and does not alter aerobic 

 glycolysis. The formation of virus in minced chorioallantoic membrane is 

 inhibited 85% by 27 mM malonate when glucose is the substrate and 95% 

 when glutamate is the substrate (Eaton and Scala, 1957). The injection 

 of 1 mg sodium malonate into chick embryos 1 hr after inoculation with 

 virus reduces the amount of virus after 48 hr by 55% (Hannoun, 1952). 

 The energy for the synthesis of new virus material must come mainly from 

 the host cell tricarboxylate cycle. It is impossible to reduce the energy 

 supply for virus synthesis without simultaneously restricting the energy 

 for host cell activities. However, it appears that the virus propagation is 

 selectively depressed because it is the most endergonic process occurring, 

 the chorioallantoic cells otherwise not being very functionally active. As 

 long as the low maintenance energy requirement is satisfied, the cells are 

 not damaged (see Fig. 1-9-6). If one were dealing with virus in an active 

 tissue, such as nerve or muscle, it would be much more difficult, or im- 

 possible, to selectively block virus multiplication. 



Other viruses growing in animal cells have been studied with various 

 results. Malonate at 6.7 mM has a definite depressant effect on the proli- 

 feration of vaccinia virus in chick embryo cultures (R. L. Thompson, 1947) 



