INTERFERENCE BETWEEN ANIMAL VIRUSES 165 



initiated with mixedly infected organs (Levaditi, 1942 a,b,c, 1943; Levaditi 

 and Henry-Eveno, 1952; Levaditi and Noury, 1943 a,b,c, 1944a,b; Levaditi 

 and Reinie, 1940, 1941; Levaditi and Vaisman, 1951a,b,c,d,e; Levaditi et al., 

 1952a,b). In absence of any quantitative evaluation, especially with regard 

 to relative rates of multiplication of the juxtaposed viruses, it is impossible to 

 relate these observations to interference. 



b. Independence of Antigenic Relationship and Antibody Production: Cross 

 Resistance and "Minor" Group Antigens. Many of the viral pairs listed in 

 Table I testify to the fact that interference can occur between antigenically 

 and taxonomically unrelated viruses. This point requires no further comment. 

 Moreover, interference in embryonated eggs or in tissue culture obviously 

 does not involve antibody production. A more subtle difficulty arises in 

 assessing the possible role of interference as a mechanism underlying induction 

 in animals of reciprocal resistance to viruses which share only some antigenic 

 properties. Specifically, what is the significance of antibodies to "minor" 

 group antigens in the evolution of resistance to heterologous viruses of a 

 single group? For example, past exposure to one type of poliovirus so sensitizes 

 monkeys or human beings that vaccination with a different type induces 

 production of neutralizing antibody against all three types (Salk, 1956). 

 Similarly, consecutive infection with different members of the arthropod- 

 borne viruses of group B which share CF and HA antigens (Sabin, 1950; 

 Sweet and Sabin, 1954; Casals and Brown, 1954) induces formation of broadly 

 cross-reacting neutralizing antibodies (Smithburn, 1954; Schlesinger et al., 

 1956; Imam and Hamrnon, 1957). 



In terms of resistance to reinfection, it is striking that monkeys vaccinated 

 with inactivated polioviruses were found protected against intracerebral 

 challenge doses of only homotypic virus (Morgan, 1949). In contrast, when 

 -polio-cotivalescent monkeys were reinoculated intracerebral^ with hetero- 

 typic strains, a considerable proportion was found resistant (Bodian, 1949). 

 Bodian observed not only an inverse relationship between the severity of 

 primary paralysis and frequency of successful heterologous reinfection, but 

 also a localization of protection to previously involved extremities. He 

 rejected interference as a basis of cross resistance because it persisted for up 

 to 13 to 22 weeks, i.e., longer than virus was then assumed to remain associated 

 with cells of the CNS. Since then, Bodian (1957) has shown that polio virus in 

 demonstrable concentrations does persist in the spinal cord of paralyzed 

 monkeys for 4 weeks. This finding, together with the demonstration of 

 interference between heterotypic polioviruses in tissue culture (see Table I), 

 offers a stronger case for the previously rejected interpretation. 



The situation may be similar in the case of types 1 and 2 dengue virus in 

 man. Sabin (1952b) found that human volunteers convalescent from infection 

 with one type acquired evanescent resistance (for about two to six months) to 



