HEMAGGLUTINATION BY ANIMAL VIRUSES 25 



Even with one donor species, there may be differences in cell susceptibility 

 to hemagglutination. With fowl cells there was only slight variation with 

 influenza viruses (Miller and Stanley, 1944) but with mumps virus a fourfold 

 range was observed (Beveridge and Lind, 1946). 



Human type A influenza strains freshly isolated in the chick amniotic 

 cavity frequently agglutinate human, pigeon, and guinea pig red cells to a 

 much higher titer than fowl cells (Burnet et ah, 1942, 1945). Such strains are 

 said to be in the phase. They grow poorly, or not at all, in the allantoic 

 cavity and have a lower avidity for the inhibitors in ovomucin and chick 

 embryo lungs (Stone, 1951). 



Virus may often be retained in the phase by passage at limit dilution but 

 Hirst (1947) has reported difficulty with this. On repeated egg passage of 

 phase virus at low dilution, genetic mutants appear and rapidly dominate the 

 population. This derived, or D phase virus, becomes the stable form on chick 

 embryo passage. Intermediate forms between and D — so-called S and o> 

 forms — may also appear during adaptation (Burnet and Stone, 1945a,b). 

 D phase virus grows well in both the amniotic and allantoic cavities and 

 agglutinates red cells of fowl, guinea pig, and human to virtually the same 

 titer (Beveridge et ah, 1944). 



Some strains, fully adapted to growth in the allantoic cavity, nevertheless 

 fail to agglutinate fowl cells to a significant titer; an example is Ian 

 (Anderson and Burnet, 1947). This strain did produce a mutant, Ian D, 

 which agglutinated fowl cells but did not overgrow Ian in the allantoic 

 cavity. In another instance, a highly egg-adapted virus, "Melbourne egg," 

 developed a hemagglutinin pattern reminiscent of virus in that it agglut- 

 inated fowl cells to lower titer than guinea pig cells (Burnet and Bull, 

 1944). A change superficially resembling the O-D transformation, but not 

 based on genetic change, can be produced in WS (type A influenza) by 

 alteration of ionic environment (Magill and Sugg, 1948; Burnet et ah, 

 1949). 



A hint of a genetic change similar to the O-D transformation was found in 

 type B virus by Burnet and associates (1944). A newly isolated strain de- 

 veloped a higher ratio between fowl and human cell agglutinating titers on 

 repeated passage. 



4. Effect on Hemagglutination of Physical and Chemical Agents 



The biological activities of an influenza virus particle may be altered by a 

 variety of physical or chemical agents. Susceptibility varies considerably 

 from strain to strain and these differences have been valuable as markers in 

 genetic experiments. In general, certain properties of the virus are altered or 

 destroyed in the same sequence by each damaging agent, a sequence first 

 established by the Henles in their work on ultraviolet irradiation. 



