RAPPAPORT, SIEGEL AND WILDMAN 



13 



fashion, and correlated with it is a proportionate increase in the amount of virus 

 which can be extracted from the dead cells. A graph showing the increase in 

 lesion area and associated infectivity is shown in figure 3. Beginning 2 days 

 after inoculation, and continuing for 5 days, both the lesion area and the infec- 

 tivity rose synchronously. Each cell produced on the average of 100,000-200,000 

 virus particles. The axial growth of the lesion during this interval was a linear 

 function of time. The data for both semi-axes of the elliptical lesion are graphi- 

 cally represented in figure 4. Given this rate of axial growth, and an average cell 

 size, it was calculated that a cell died and was added onto the periphery of the 

 lesion approximately every 3 hours. 



To the unaided eye, the lesion appears sharply demarcated, but microscopic 

 observations reveal degenerative changes in approximately 3-4 cells beyond the 

 necrosis. Assuming that these changes are associated with virus infection, one 



3.0 



2.5 - 



2.0 - 



Fig. 4. Increase in axial length of 

 lesion. Major serai-axis, A; minor semi- ^3 

 axis, B. 



1.0- 



0.5- 



may say that between 12 and 16 hours elapse from the moment of infection to 

 cell death. This 3-4 cell perimeter of degenerate cells has a further and more 

 important bearing on our concept of the intracellular virus. Although large 

 amounts of such tissue have been carefully dissected away from the necrotic area 

 and tested for virus activity, little or no infectivity could be demonstrated. The 

 suggestion from the radiation studies, that the intracellular reproducing unit 

 may be different from the in vitro virus, finds its counterpart here in these 

 degenerate cells. The disease is present, yet few or no particles capable of initiat- 

 ing a new infection can be recovered. It is as if the invasion of tissue and the 

 spread of the necrosis to cells other than the inoculated cell was accomplished by 

 some more elementary reproducing unit, and that later, perhaps just before cell 

 death, the rods which typify extracellular TI\IV make their appearance. Con- 

 ceivably, then, the characteristic in vitro rod may be but the end product of 



