48 HIRST 



of substances of different configurations, each part of the complex hav- 

 ing different affinities for various strains and different susceptibilities 

 to destruction. The pattern of such a complex may vary even among 

 cells from different birds of the same species. The question of virus 

 enzyme specificity is further amplified below. 



Studies on the specificity of the virus enzymes and of substrate have 

 been carried out with inhibitors from various sources. These have the 

 advantage that rates of destruction can be more carefully measured 

 than is possible with cell bound receptors (Hirst, 1950''). When ma- 

 terial from a biological source (A) is tested for inhibitor content with 

 a number of different strains (1, 2, 3, etc.) enormous variations (200 

 fold or more) in titer are found. Material from another source (B) 

 also shows such variations and the amounts of different inhibitors found 

 differ both relatively and absolutely from those of source A. (Inhibitor 

 A may give titers of 1000 with strain 1 and 10 with strain 2, while 

 B may have a titer of 50 with 1 and 500 with 2.) One way to interpret 

 these findings is to assume that there are a number of active molecular 

 species present in different proportions in the two samples. By meas- 

 uring the rate of destruction of these inhibitors with different strains 

 one obtains further information on this point: 



(1) The inhibitors in preparation A are destroyed progressively 

 by viruses and the inhibitor for strain 1 disappears at a faster rate than 

 that for strain 2, etc., just as happened with red cell receptors. 



(2) The order in which inhibitors disappear with virus action is 

 characteristic for the source of inhibitor. However, this order may be 

 completely inverted when material from another source is tested. (With 

 preparation A the inhibitors for various strains may disappear in order 

 1, 2, 3, 4 and 5, while wdth B the order may be 5, 4, 1, 3, 2.) 



(3) The order of inhibitor destruction is not, in general, affected 

 by the strain used for destruction. If with preparation A, strain 5 in- 

 hibitor disappears more slowly than that of any other strain, the same 

 holds even when strain 5 is used for destroying inhibitor activity. In 

 this approach there is no strain specificity on the part of virus enzymes. 



(4) There are marked differences in the speed with which differ- 

 ent viruses destroy an inhibitor and in this there is some parallelism 

 with the position of the strain in the receptor gradient. 



(5) There are some exceptions to the statement about enzyme 

 specificity in (3). Almost all strains, given sufficient time and when 

 present in adequate concentration, can destroy the receptor complex 

 completely (i.e. destroy the inhibitor active against any and all strains). 



