INHIBITION OF MULTIPLICATION 213 



In the absence of studies on inhibition of virus multiplication in single 

 infected cells, it is uncertain how much validity should be ascribed to results 

 that point toward inhibitory effects after the expiration of the latent period. 

 With animal viruses, inhibition studies have so far been done with either 

 intact tissues or large populations of cells in culture. Purposeful synchroniza- 

 tion of infection has been attempted only with influenza A virus by means of 

 pretreatment of tissue with methoxinine (Ackermann and Maassab, 1954b). 

 In other instances, there is the likelihood that various steps in the complex 

 process occurred at different rates in different cells and that this asynchronism 

 affected results in multicellular systems. It should be emphasized that the 

 latent period is defined as the interval before any new infective virus particles 

 appear. It is, therefore, a measure of the time required to produce new particles 

 by the first cells to yield. This is a minimal rather than a mean value; later 

 yielding cells obviously may have longer latent periods than those that first 

 produce new particles. 



2, 5-Dimethylbenzimidazole (MB) caused definite inhibition of multiplica- 

 tion of influenza B virus in single-cycle experiments, even when added at 4 or 

 5 hours after inoculation (Tamm et ah, 1953a; Tamm and Tyrrell, 1954). In 

 the host tissue system used, the latent period of the virus is probably less than 

 4 hours (Tamm and Tyrrell, 1954). The compound appears therefore to have 

 been inhibitory for at least one hour after the end of the latent period, even 

 though the extent of the inhibition produced was not large. 



Caprochlorone appears to have caused some inhibition of multiplication of 

 influenza A virus in single-cycle experiments, when added 4 hours after 

 inoculation (Liu et ah, 1957a). In the host tissue used, the latent period of the 

 virus is almost certainly less than 4 hours (Liu et ah, 1957a). The amount of 

 inhibition produced was appreciable. 



A chloro-arabinopyranosyl derivative of benzimidazole (DAB) caused marked 

 inhibition of multiplication of polio virus, type 2, in single-cycle experiments, 

 even when added 5 hours after inoculation (Nemes and Tamm, 1958). The latent 

 period of the virus, in the host cell system used, is about 4 hours (Fogh, 1955). 



Although the mechanism of inhibition is not known for MB or caprochlorone, 

 there is information regarding it for DAB. Not only does the compound 

 interfere with the synthesis of RNA but also it inhibits the synthesis of 

 protein (Nemes and Tamm, 1958). As indicated in the preceding section, this 

 activity contrasts sharply with that of DRB, which interferes primarily with 

 RNA synthesis and is inhibitory only during the first half of the latent period 

 (Nemes and Tamm, 1958). 



IV. Inhibition of Release 

 In most instances studied, animal virus particles appear to be liberated or 

 released from infected host cells at a relatively slow rate (Cairns, 1952; 



