HEMAGGLUTINATION BY ANIMAL VIRUSES 39 



on the structure of the whole virus surface, and determines the place of the 

 virus in the receptor gradient. 



When all the red cell receptor areas have been browsed over in this way, 

 the virus must leave the red cell. It is possible for a virus with greater 

 affinity for red cells — one further down the gradient — to adsorb to these 

 treated red cells, to alter a proportion of the remaining substrate groupings, 

 and to elute in its own turn. On this basis the receptor gradient is explained. 



As an alternative to the idea of browsing, Sagik et al. (1954) have pro- 

 posed that a virus on the red cell may "act at a distance" in a fashion similar 

 to that demonstrated for phage on bacteria. 



Indicator virus possesses no active enzyme and does not elute from a sus- 

 pension of red cells, but fresh virus or RDE added to the suspension will 

 remove the indicator virus. This would be due to the alteration by the added 

 enzyme of the necessary proportion of substrate groupings adjacent to the 

 attached indicator virus. It seems necessary to assume that the production 

 of the indicator state alters the virus surface to give it a relatively greater 

 affinity for soluble mucoid inhibitor than for red cells (Anderson et al., 1948). 



It is readily agreed that since periodate alters substrate groupings, 

 periodate-treated receptors will not permit virus elution through enzymatic 

 action. 



2. Hypothesis of Enzyme Substrate Attraction 



This would regard union of virus and receptor as due primarily to union 

 between the functional group of the virus-enzyme and the substrate groups 

 in the receptor mucoid and would regard the part played by other com- 

 ponents of the two surfaces as being concerned only in determining the 

 mutual accessibility of virus enzyme and cell substrate groups (Hirst, 

 1942b; Burnet, 1948c, 1951b; Burnet and Lind, 1950; Chu, 1948d). 



Explanations of browsing and elution would follow as before, but the 

 receptor gradient is interpreted in terms of receptors on the red cell which 

 are of varying accessibility to different viruses (Burnet et al., 1945). 



The enzyme on indicator virus is claimed to be so modified as to be in- 

 capable of elution but still to retain the pattern needed for it to unite with 

 substrate groupings on the red cell. It is difficult, on this basis, to explain the 

 ready removal of indicator virus by RDE or live virus. Receptor mucoid, 

 partly altered by potassium periodate, would similarly bind virus enzyme 

 but not allow completion of enzymatic action or elution. 



In nearly every case, the development of an indicator state in treated virus 

 is strictly correlated with loss of enzyme activity of the virus on the inhibitor 

 concerned. This has been advanced in support of the hypothesis of enzyme 

 substrate attraction as the mechanism of hemagglutination, but it also 

 appears compatible with the first hypothesis described above. 



