Chemical Inhibition of Viruses 161 



particles, which are considerably more complex in con- 

 stitution and are thought to contain both proteins and 

 nucleic acids. This is dissimilar to the effect of proflavine 

 on the reproduction of phage, which appears to be directed 

 mainly against the final assembly of mature virus particles 

 from a number of preformed components (13). It differs also 

 from the effects of 5-methyl tryptophane or chlorampheni- 

 col on phage multiplication, which are considered to result 

 chiefly from inhibition of protein synthesis (5, 10). 



If the reproduction of animal viruses is more nearly com- 

 parable to that of microbial species than to the stepwise 

 intracellular process now envisioned for phage, the results 

 obtained with the chloro-substituted benzimidazole ribo- 

 side may not be surprising. Under these circumstances, it 

 might be expected that inhibition of reproduction would 

 be associated with a proportional reduction in all sub- 

 stances found in the virus particle. If, however, reproduc- 

 tion depends on the production of individual components 

 separately and their eventual assembly into mature in- 

 fective particles, it would seem probable that some com- 

 ponent should accumulate when an inhibitory compound 

 is present. There is, so far, no decisive evidence that this 

 occurs with animal viruses. 



Inhibitors as Chemofherapeufic Agents 



In infections with animal viruses, but not with phage, it 

 is necessary to be concerned with the responses of a society 

 of cells to the results of the reproductive process. Such a 

 community of cells, often of widely dissimilar kinds, con- 

 stitutes a tissue, and it is the response of tissues that leads 

 to reactions recognizable as disease. In nature, the number 

 of infective virus particles that first succeed in reaching 

 susceptible cells in a given tissue is probably relatively 

 small. The long incubation periods associated with many 

 virus diseases are in accord with this idea. It is well known 



