12 F. M. BUENET AND W. M. STANLEY 



The concept of the cell surface more or less modified by infiltration with 

 viral components, being used to form the outer surface of the virus is in most 

 respects a simple spatial and morphological one. 



As each reproducible j)henomenon is recognized and attempts made to 

 define the parameters that influence its manifestations, new aspects suscept- 

 ible to a greater or lesser degree of quantitative investigation will emerge. 

 This potentiality of infinite elaboration, once any new phase of biological 

 study is initiated, is at once an opportunity and an obstacle. The oppor- 

 tunity arises when some aspect of the biological phenomenon appears clearly 

 capable of analysis by chemical or physical techniques to give an interpreta- 

 tion expressible in terms of established concepts. In the case of influenza 

 virus, the recognition by Hirst (1941) that "receptors" on the red ceU were 

 destroyed by what must be an enzyme associated with the virus, led after 

 some years and a tortuous course of investigation to Burnet and Stone's 

 (1947) recognition of the existence and usefulness of the receptor-destroying 

 enzyme of Vibrio cholerae, and eventually to the synthesis of neuraminic acid 

 and the demonstration that purified influenza virus will quantitatively spht 

 the acetylgalactosamine neuraminic acid compound (Gottschalk, 1957; 

 Cornforth et al, 1958). 



It seems unlikely that the enzymatic action of influenza virus will now 

 attract many other virologists to its investigation at the physicochemical or 

 enzymological levels. Yet it is still perfectly evident that there is an infinitude 

 of work to be done on this tiny facet of influenza virus activity, at this par- 

 ticular level. What, for instance, is the nature and distribution of the neur- 

 aminic acid compounds on the red ceU surface, what is the basis of the 

 receptor gradient, of its association with change in the electrophoretic 

 mobility of cells treated by virus? What change occurs in the virus enzyme 

 to produce the "indicator" state on heating virus preparations, what allows 

 irreversible union to the cell under certain circumstances, why do Newcastle 

 disease and mumps viruses give rise to hemolysis apparently by a similar or 

 the same enzymatic mechanism? These points refer only to the model reac- 

 tion between virus particle and red ceU. The surface of the susceptible cell is 

 clearly more complex and labile and, in the allantoic cavity at least, plays 

 demonstrably important roles both in allowing the occurrence of infection 

 and in the final fabrication and liberation of the new brood of infective 

 units. 



Perhaps it wiU underline the complexity and the difficulty of a general 

 approach to recall that aU these problems of the interaction between influenza 

 virus and cell surface have emerged only because the special type of hemag- 

 glutination shown by influenza and related viruses provides a uniquely 

 favorable tool for the technical approach. Every other type of virus prob- 

 ably has an equally complex and subtle approach to the surface of the cell 



