254 T. FRANCIS, JR. 



The complement-fixing antigen common to the type A strains (type- 

 specific) differs from that of type B and may be used for typing of strains 

 when immune serum to the test strain is not available. It may be found in 

 fluids as "soluble" antigen. Strain-specific complement-fixing antigen is 

 probably the same as the hemagglutinin of the virus particle. Some investiga- 

 tors have found it sufficiently distinctive as to parallel the specificity of 

 hemagglutination or neutralization. The hemagglutinating mucoprotein 

 combines specifically with antibody and appears to be an essential parti- 

 cipant in the infectious process. The character of primary and secondary 

 antigens, their number and composition would then be considered as varia- 

 tions within the molecular configuration of these hemagglutinating units. 

 The host and his immune state may exert a significant influence upon their 

 make-up, hence upon the character of the virus strain. The RNA is considered 

 to be the basic genetic replicating component. Its role in infection and 

 immunity is uncertain. The presence in virus preparations of components 

 derived from the host tissue introduced antigens which can give common but 

 extraneous serological reactions, whether they are integrated into the virus 

 or are merely contaminants. 



B. Serological Types 



Three immunologically distinct types of influenza virus, A, B, and C, have 

 been generally acknowledged because of their association with human disease 

 of related clinical nature, their comparative behavior in other hosts, and the 

 similarity of their action in hemagglutination. It has been proposed for 

 similar reasons that the Sendai virus or hemagglutinating virus of Japan 

 (HVJ) (Kuroya et al., 1953) be considered type D (Jensen et al., 1955; Francis, 

 1955). This has been supported by Russian investigators, who observed an 

 epidemic of influenza in 1956 in which this virus was involved (Gerngross, 

 1957; Gorbunova et al., 1957). More recently Chanock and others (1958) have 

 reported isolation of the agent from children in the United States. In addition, 

 they have encountered another agent in outbreaks of respiratory illness 

 resembling influenza, which they tentatively suggest may be a type E. 



C. Antigenic Analysis of Type A Strains 



1. Studies with Sera of Experimental Animals 



a. Initial Studies in Mice (1935-38). Influenza A has been the most fre- 

 quently epidemic since 1933, when the virus was discovered by Smith and 

 associates (1933). Strains of the same virus were then isolated in North 

 America (Francis, 1934) and in Australia (Burnet, 1935). The swine influenza 

 virus (Shope, 1931) was readily recognized by active immunity tests to be 

 related, but different serologically. Its relationship to strains from man was 



