162 Perspecf'ives in Microbiology 



that, in experimental animals, the time before gross evi- 

 dence of infection appears is inversely related to the num- 

 ber of infective particles inoculated. Virus reproduction 

 occurs during the incubation period, and the concentration 

 of new virus particles in an infected tissue increases at a 

 logarithmic rate prior to the appearance of symptoms or 

 signs recognizable as disease (22, 29). 



The quantitative relationship between virus concentra- 

 tion and gross lesions, as a function of time after inocu- 

 lation, is especially well seen in respiratory virus diseases 

 in the mouse. With both influenza virus (22) and pneu- 

 monia virus of mice (29), considerable quantities of virus 

 appear in the lung before gross lesions develop. There- 

 after, virus concentration continues to increase at a more 

 rapid rate than do lung lesions. Thus, much virus reproduc- 

 tion has occurred before the existence of the infection can 

 be suspected on gross examination. If all the multiplication 

 an infected tissue could support were completed before 

 evidence of disease appeared, it would seem obvious that 

 there could be no hope that substances which inhibit re- 

 production could be effective as chemotherapeutic agents. 

 Only a fraction of the maximal virus concentration is pres- 

 ent, however, when gross lesions appear, and more repro- 

 duction occurs as the extent of the lesions increases and the 

 disease progresses (22, 29). There should be, then, an inter- 

 val after recognition of the disease during which inhibition 

 of virus reproduction could modify the course of the dis- 

 ease. 



This hypothesis has been subjected to direct test in in- 

 fections with pneumonia virus of mice, using K. pneu- 

 moniae capsular polysaccharide as a chemotherapeutic sub- 

 stance (23). A total of 20 |ig of the polysaccharide given 

 either two or three days after inoculation with the virus 

 converts a uniformly fatal disease into one from which the 

 great majority of animals recover. This result is obtained 

 not only when virus reproduction is in the logarithmic 



