BIOLOGICAL ASPECTS OF INTRACELLULAR STAGES OF VIRUS GROWTH 135 



point is further discussed in Section V). This suggests that the exponential 

 rise in the amount of intracellular infective virus reflects a logarithmic rate of 

 increase of one virus precursor, whose rate of production limits the rate of 

 production of mature infective virus forms. 



C. Influenza Virus 



Henle et al. (1947) carried out one-step growth curves of influenza A and B 

 viruses in the allantoic cavity of the chick embryo, using a large dose of 

 ultraviolet irradiated heterologous virus as an interfering agent, to prevent 

 the occurrence of a second cycle of virus growth. The validity of this tech- 

 nique depends on whether the irradiated virus can be used to prevent a 

 second cycle of virus growth without inhibiting the first cycle. In their paper, 

 Henle et al. (1947) thought that the irradiated virus interrupted the readsorp- 

 tion of virus released in the first cycle, but, since the irradiated virus was given 

 1 hour after the live virus, it may have also induced some interference in the 

 cells initially infected. Hence the appearance of a step in the growth curve 

 described by Henle et al. might be to some extent artificial, and indeed, in 

 later work, Henle and associates (1954) showed that virus continued to be 

 released from infected cells over a period of 30 hours or more. With this 

 limitation, the results of Henle and his co-workers show that for the PR8 

 strain of influenza A, after a lag period of 6 hours, new virus was released into 

 the allantoic cavity within the next 2 hours with an average value of 63 ID 50 

 produced per ID 50 of virus adsorbed. The corresponding figures for the Lee 

 strain of influenza B were 36 ID 50 produced per ID 50 adsorbed after a lag 

 period of 9 hours. Henle and Rosenberg (1949) later extended these findings 

 to other strains of influenza A and B and found that, in general, the influenza 

 B viruses showed a longer lag period and a lower viral yield than the A strains. 

 However, if in fact the viral interference is induced at a constant time after 

 inoculating the irradiated virus, the apparently lower yield may simply reflect 

 a slower rate of growth of the B viruses and it is known that the yield of some 

 influenza B strains per egg is not significantly less than for A viruses. 



Cairns (1952) studied the release of influenza A virus hemagglutinin into 

 the allantoic cavity and used the V. cholerae enzyme, RDE, to prevent 

 readsorption of newly released virus. Viral hemagglutinin was first liberated 

 after 5 hours but the 50 % liberation time, i.e., the time at which half the 

 ultimate first-cycle yield of virus had been liberated, appeared to be about 8 

 hours. Cairns also measured the amount of virus liberated in each half-hour 

 period ("differential response") in this system and found that periods of peak 

 liberation of virus occurred at 7^-9 hours, 14-14^ hours, and about 19 hours. 

 He interpreted these findings in terms of cycles of virus growth, of which the 

 first cycle lasted longer than succeeding cycles. However, it was later found 

 that infected cells continue to liberate influenza virus over long periods of time 



