138 ALICK ISAACS 



membrane at the same time, the proportion being about 1 % at 3 days; even 

 at 7 days it was less than 10 %. Maitland and Magrath (1957) have also studied 

 the growth of this virus in pieces of chorioallantoic membrane suspended in 

 vitro, as well as in minced chick embryo and chick embryo cell suspensions. 

 The increase in infectivity was variable from one experiment to another but 

 tended to be more nearly exponential than linear. 



In reviewing studies of growth curves for such different viruses grown 

 under varying cultural conditions it is surprising to find so many similarities. 

 After a lag period, all the viruses studied have shown an exponential increase 

 in titer for part of their growth cycle. Also, there is a suggestion that those 

 viruses which have a longer lag period have a slower rate of increase of viral 

 infectivity. It is surprising, too, how frequently a rate of increase of infectivity 

 of the order of about one log i0 per hour has been reported, i.e., for polio- 

 myelitis (Dulbecco and Vogt, 1955), western equine encephalitis (Rubin et al., 

 1955), influenza (Henle et al., 1947; Ledinko et al., 1957), and Newcastle 

 disease virus (Rubin et al., 1957). It is interesting to note that all these 

 viruses contain ribonucleic acid (RNA); on the other hand, herpes simplex 

 and vaccinia, probably both DNA viruses, seem to have a longer lag period 

 and a slower rate of growth. It is worth speculating whether the rate of 

 growth of these different viruses may depend on the rate of synthesis of the 

 different nucleic acids in infected cells. 



V. The Release of Virus from Infected Cells 



It is striking in comparing growth curves for different animal viruses to 

 note great differences in the ratio of extracellular to cell-associated virus titer 

 during the period of exponential increase of virus, e.g., for western equine 

 encephalitis virus the extracellular virus titer was ten times greater than the 

 cell-associated virus titer, whereas for vaccinia virus the extracellular virus 

 was only 1/100 of the titer of cell-associated virus. These differences clearly 

 reflect major differences in the rate at which fully infective virus is released 

 from cells after it is formed. In this section the rate of release of different 

 viruses is compared in order to gain some insight into the mechanism by 

 which virus is liberated from infected cells. 



A. Western Equine Encephalitis and Poliomyelitis Viruses 



In studying the release of western equine encephalitis virus from individual 

 cells, Dulbecco and Vogt (1954) found that by 4 hours, 60 % of cells had 

 released small amounts of virus, i.e., were low yielders, whereas by 7 hours, 

 only 11 % of the cells were low yielders, the other cells now giving high 

 yields of virus. This finding implies that cells were continuing to release virus 

 over the period 4-7 hours, i.e., individual cells release virus over a long period 



