INHIBITION OF MULTIPLICATION 209 



In contrast, the multiplication of vaccinia virus, which contains deoxy- 

 ribonucleic acid (DNA) (Hoagland et al., 1940; Peters and Stoeckenius, 1954), 

 is not inhibited more effectively by /3-D-ribofuranosides of chlorobenzimi- 

 dazoles than by the halogenated benzimidazole without the ribose carbo- 

 hydrate moiety (Tamm and Overman, 1957). Furthermore, it appears that 

 DRB does not inhibit the synthesis of DNA in concentrations at which 

 synthesis of RNA is markedly reduced (Allfrey, 1958). This suggests that 

 relative susceptibility to inhibition by DRB may reflect the nature of the 

 nucleic acid hi the virus particle (Tamm and Nemes, 1957). 



5. 'p-Fluorojphenylalanine (FPA) 



This compound inhibits the multiplication of poliovirus, type 3, in HeLa 

 cell cultures in vitro (Ackermann et al., 1954). In single-cycle multiplication 

 experiments, 0.1 mg per milliliter of the compound completely suppressed 

 multiplication of the agent when the inhibitor was added at 1 or 2 hours. 

 It was much less effective when added at 3 hours and caused no inhibition 

 when added at 4 or 5 hours. On the basis that the latent period of this virus 

 in HeLa cells is about 4 hours (Ackermann et al., 1954), the compound is 

 most effective during the early part of the period and is ineffective during the 

 last half of the interval. 



FPA does not inactivate the infectivity of poliovirus in vitro (Ackermann 

 et al., 1954) and probably does not interfere with the initiation of the incipient 

 stages of infection. The compound inhibited the multiplication of HeLa cells 

 but did not destroy their viability, for a normal rate of cell multiplication was 

 observed on removal of the inhibitor. 



The inhibitory effect of FPA on poliovirus multiplication is completely 

 reversed by phenylalanine if the amino acid is added within 6 hours, but not 

 later, after inhibition has been induced (Ackermann et al., 1954). These data 

 suggest that some function of phenylalanine is inhibited by the metabolic 

 antagonist, FPA, and that this function is required only in an early stage of 

 the multiplication of the virus. 



Although the compound effectively inhibited poliovirus multiplication, 

 it did not prevent the cytopathogenic effect of the virus. It should be pointed 

 out that, at the concentration used, the compound itself caused some altera- 

 tion in the morphology of the host cells. Disintegration of infected cells 

 proceeded at the ordinary rate, without any increase of the infectious agent 

 (Ackermann et al., 1954). This was taken to indicate that the process leading 

 to virus multiplication and to cellular injury possess a significant degree of 

 autonomy. These results are closely similar to those obtained earlier in 

 inhibition experiments with proflavin and bacterial virus, T2 (Foster, 

 1948). 



VOL. Ill — 14 



