38 S. G. ANDERSON 



adsorb to each red cell, although Chesbro and Hedrick (1957) have speculated 

 otherwise. 



Two hypotheses have been proposed to explain virus adsorption to the red 

 cell. Both were developed in the absence of knowledge about the nature of 

 the substrate of the virus enzyme and there is still very inadequate know- 

 ledge of the detailed structure of either of the two surfaces concerned. With 

 the development of a more rigorous experimental approach, it is likely that a 

 much more satisfactory interpretation in physical terms will be available for 

 the physical aspects of the hemagglutinating process. For the present, 

 however, both theories will be described briefly, and an explanation will be 

 attempted, in terms of each theory, of certain facts of the relationship 

 between virus and red cell. The truth may well be a compromise between 

 these two theories. 



1. Hypothesis of Physical Adsorption 



This hypothesis distinguishes clearly between adsorption of virus and sub- 

 sequent enzymatic reaction. The red cell receptor is considered to be an area 

 considerably larger than the virus particle, and to contain a large number of 

 mucoid substrate groupings. The active groups of the virus enzyme might 

 form only a limited portion of the virus surface (Anderson, 1947b). 



Adsorption is considered to be a function of all of the virus surface which 

 is opposed to the red cell, and also of a comparable portion of the receptor 

 area, including both substrate groupings and other red cell structures not 

 susceptible to alteration by virus enzyme. 



Adsorption of influenza virus would correspond with the adsorption onto 

 red cells of other viruses, such as Japanese B encephalitis and GD VII, where 

 no virus enzyme enters into consideration. Myxoviruses would differ only in 

 the fact of subsequent elution through receptor destruction. 



In support of this hypothesis is the ready removal of influenza virus from 

 red cells, without receptor destruction, by raising the ionic level of the 

 medium (Hirst, 1949). There is also the finding of Tamm (1954a) of reversible 

 union of LEE virus with cat erythrocytes. Virus can be recovered from cat 

 erythrocytes, again without receptor destruction, by raising the temperature 

 from 5 to 24°C. in a suitable ionic medium. 



It is assumed that, after adsorption, a virus becomes orientated so that the 

 enzyme reacts with mucoid substrate in the vicinity; and that each time one 

 substrate grouping is enzymatically altered the local attractive forces between 

 red cell and virus are diminished. When a sufficient proportion of groupings 

 in the vicinity has been altered, the virus particle is believed to roll or slide 

 to an adjacent portion of the receptor area or to a nearby receptor area. This 

 phenomenon has been termed "browsing." This "sufficient proportion of 

 groupings" in any one area is a characteristic of the virus strain; it depends 



