132 ALICK ISAACS 



the other two antigens (Henle et al., 1954). As between soluble antigen and 

 hemagglutinin, Hoyle (1948) found that soluble antigen appeared first, while 

 Fulton (1949) found that the two appeared simultaneously. It is important in 

 making this comparison to be sure that the inhibitor of viral hemagglutina- 

 tion present in susceptible cells is completely inactivated; when this precau- 

 tion was taken there was no difference between the time at which hemagglu- 

 tinins and soluble antigen could be first detected (Liu and Henle, 1951; 

 Burnet and Lind, 1954). It seems that the evidence that the soluble antigen 

 appears before the hemagglutinin in infected cells is not definite. 



C. Cell-Associated Antigens of Other Viruses 



In almost all viruses which have been investigated, small particle antigens, 

 detectable by complement fixation and usually called soluble antigens, have 

 been found associated with viral multiplication. It has generally been found 

 that these antigens remain intracellular, that they are distinctly smaller than 

 the virus elementary bodies, and that they have less serological specificity 

 than the elementary bodies. 



There are at least two distinct cell-associated antigens of vaccinia virus, 

 the soluble LS antigen (Craigie, 1932), which is a protein, and the hemagglu- 

 tinin (Nagler, 1942), a lipid-protein complex. During the growth of the virus 

 these antigens increase in amount parallel to the increase of viral infectivity 

 (Metcalf, 1955; Maitland and Tobin, 1956) and there is no evidence of their 

 appearing before mature virus or of their being used up to produce new virus. 

 A soluble antigen is produced during the growth of herpes simplex virus 

 (Hayward, 1949) but there is no evidence for its preceding the appearance of 

 infective virus (Scott et al., 1953; Modi and Tobin, 1954). Van den Ende and 

 co-workers (1957) studied the soluble (12 nut) antigen which develops in the 

 brains of suckling mice infected with rabies virus. The antigen appeared after 

 the rise in titer of infective virus and apparently continued to increase in 

 amount after the maximal infective titer was reached. Differences in sensi- 

 tivity of infectivity and complement fixation titrations affect the interpreta- 

 tion of all these results but there is no support for the idea that soluble 

 antigens in general appear in cells before mature virus. 



Among the smaller viruses, poliomyelitis (Selzer and Poison, 1954), 

 African horse sickness (Poison and Madsen, 1954), and foot-and-mouth 

 disease (Bradish et al., 1952) viruses have all been shown to produce soluble 

 complement-fixing antigens of small particle size; Poison has drawn attention 

 to the fact that the estimated particle size for the soluble antigens of many 

 different viruses is about 12 m/x. Apart from this, there is no evidence to suggest 

 whether the soluble antigens of different viruses have a similar function 

 or are produced by analogous processes. There is, however, an interesting 



