BIOLOGICAL ASPECTS OF INTRACELLULAR STAGES OF VIRUS GROWTH 113 



a large proportion of the virus taken up. Since most studies with animal 

 viruses have not been carried out with isolated cells, two interpretations of 

 these results are possible. In the first, it is assumed that the virus which is 

 detectable during the lag period is the parent of the new virus produced, and 

 the virus which is not detectable has been destroyed by the cells and plays no 

 further role in multiplication. In the second interpretation it is thought that 

 the virus which is detectable during the lag period is adventitious, while the 

 virus which has become undetectable has entered the eclipse phase on the 

 road to producing new virus. It is also possible that the process is not uniform 

 throughout animal viruses, although it would obviously be preferable to try 

 to fit the experimental results into a single theoretical framework. We may 

 therefore consider separately the following questions. 



1. How much of the infectious virus taken up by the cells is recoverable 

 during the lag period? 



2. What happens to other viral properties, e.g., antigenic properties, 

 during the lag period? 



3. What is the significance of the infective virus which is detectable during 

 the lag period? Thereafter, we may try to arrive at an assessment of the idea 

 of an eclipse phase as a general phenomenon among animal viruses and as an 

 essential stage in the multiplication process. 



It is perhaps unfortunate that more work on the multiplication of animal 

 viruses has been carried out on influenza and related viruses than on any 

 others, but an attempt will be made to balance observations on influenza 

 viruses with the findings in regard to smaller viruses, e.g., poliomyelitis and 

 the encephalitis viruses and larger viruses, such as vaccinia and herpes 

 simplex. 



A. Amount of Infective Virus Recoverable during the Lag Period 



1. Bacteriophages 



As a standard with which to compare animal viruses, the experiments of 

 Doermann (1952) on the eclipse phase of bacteriophages should be quoted. 

 Doermann studied coliform bacteria infected with T4 phage. At intervals 

 after infection the bacteria were lysed by applying a large dose of heterolo- 

 gous phage along with cyanide to stop further phage synthesis, a treatment 

 which was shown to liberate as much phage during the terminal stages of 

 intracellular development as occurs naturally. When bacteria were infected 

 at a multiplicity of 1, lysis at 10-J- minutes after infection revealed less than 

 0.01 % of the final yield, or less than 1 phage particle in 80 bacteria. Clearly, 

 therefore, the eclipse phase in its strictest sense implies that cells which are 

 known to be infected with virus and which would have produced new virus if 

 they had been left, show no infective virus during the lag period. 



VOL. III.— 8 



