BIOLOGICAL ASPECTS OF INTRACELLULAR STAGES OF VIRUS GROWTH 141 



surface. The results are strikingly similar to those obtained by Cairns and 

 Mason for influenza virus. 



C. Herpes Simplex and Vaccinia Viruses 



In their studies of herpes simplex virus, both Scott et al. (1953) and Wildy 

 (1954) noted that the titer of released virus was about one log 10 less than that 

 in the cells during the period of exponential increase in virus titer. Similarly, 

 for vaccinia virus, Overman and Tamm (1957) found that during the period 

 of exponential increase less than 1 % of the virus in the membranes was 

 released into the medium. It is clear, therefore, that herpesvirus and vaccinia 

 viruses, once formed, are only slowly released from the cells. Calculation of 

 the release time would not be meaningful, however, since pock-producing 

 viruses such as these probably spread from cell to cell without being liberated 

 into the medium. Andrewes (1930) showed that herpesvirus could continue to 

 grow in tissue culture in the presence of immune serum, which, however, 

 prevented the initiation of infection and Black and Melnick (1955) noticed 

 that herpes B virus grown in monkey kidney cells was able to form plaques 

 even without an agar overlay. Primary plaques could not be prevented from 

 developing by immune serum given shortly after the virus but the serum 

 prevented the appearance of further plaques. By contrast, poliomyelitis virus 

 grown in the same cells did not form plaques and immune serum could avert 

 the spread of the virus even when infection was well under way. From what 

 is known of influenza virus, it behaves very like poliomyelitis virus in this 

 respect. We have, therefore, two contrasting modes of virus release and 

 spread. In the first, exemplified by poliomyelitis, virus is rapidly released from 

 cells once it is formed and spreads to new cells mainly by invasion via the 

 medium. In the second, exemplified by B virus, virus is slowly released from 

 cells once it is formed and can spread to neighboring cells by direct cell-to-cell 

 spread. Cell-to-cell spread presumably occurs with varicella virus too, since 

 Weller (1953) found that passage could be effected only by cell extracts and 

 not by the fluid phase. For four different adenoviruses, Ginsberg (1957) has 

 also provided evidence of slow release of virus from these cells. Once more, it is 

 interesting to note that the division of animal viruses into those which are 

 released rapidly from cells and those which are released more slowly corres- 

 ponds (so far as it is known) to viruses which contain RNA and those which 

 contain DNA. A possible division in terms of size alone is ruled out by the fact 

 that the adenovirus, a DNA virus, is slightly smaller than influenza virus. 

 At the moment, there is little guide to the possible significance of this 

 observation, and, indeed, it is difficult to be sure of its accuracy, since the 

 different viruses have not been studied under comparable conditions. 

 However, this may be an interesting generalization and it seems important to 

 see how far it is applicable among the animal viruses. 



