252 T. FRANCIS, JR. 



the pathogenesis of the viral infection upon the durability of immunity. The 

 numerous recurrences of human influenza with repeated illness in the same 

 individuals had led to accurate postulates of multiple strains in the suspected 

 virus. Once serological variants of influenza virus were demonstrated, the 

 gates were opened to the recognition of an interminable flow of antigenic 

 alterations, naturally or artificially induced. In a reverse manner, expanding 

 study of arthropod-borne animal viruses has brought together numerous strains 

 of apparently different origin and nature into serologically related groups for 

 which arthropods and lower vertebrates constitute major reservoirs. New 

 families of viruses with numerous members and subgroups have been formed 

 by virtue of common and distinct antigens, i.e., Coxsackie viruses, adeno- 

 viruses, and ECHO viruses. In these, again, clinical and epidemiological 

 features of their behavior have served as pointers to their serological 

 similarities and differences. Still other older viruses, such as poliomyelitis, 

 have been divided into separate types with recognized epidemiological 

 differences in behavior. Serological variation is now the rule among animal 

 viruses rather than the exception, as was true twenty-five years ago. 



Much of this development has been closely related to great improvement in 

 techniques which provide high concentrations of virus without large masses of 

 foreign protein, in the greater opportunity for quantitative studies, and in 

 the greatly enlarged body of investigators concerned with the biological 

 relationships among viruses which are causative agents of disease. Con- 

 sequently, the disease manifestations with which the viruses are associated 

 constitute a primary focus from which variations can be observed, while 

 relationships among viruses from apparently divergent disease states are 

 based on biochemical characteristics which determine their serological or 

 cytopathological behavior. Conversely, the range of deviation from a common 

 biochemical base will express the group boundaries. Thus, any aberration 

 from the prototype represents a variant, but because of the unstandardized 

 conditions under which differences are observed, their meaning is at times 

 uncertain. 



II Serological Reagents 



Serological behavior of viruses, as with other antigens, is the resultant of a 

 number of influences which participate in the reaction. It embraces the 

 nature and source of the agent, the character and origin of the serum, and 

 the method of measurement itself. 



The virus preparation is ordinarily a collection of particles which may 

 possess different degrees of reactivity. The size of the inoculum used can 

 affect the amount of noninfective virus present that can combine with 

 antibody, but is not reflected in titrations of infectivity. The nature of the 



