168 R. W. SCHLESINGER 



a. Distinction from Immunological Phenomena. In the classic studies by 

 Hoskins (1935) and by Findlay and MacCallum (1937) on interference by 

 neurotropic with viscerotropic yellow fever virus, a major element in ruling 

 out immunological mechanisms was the cross-protection, achieved in similar 

 manner, between yellow fever and Rift Valley fever (RVF) viruses. In other 

 cases, e.g., in the "Konkurrenz-phanomen" of Magrassi (1935) between non- 

 encephalitogenic and encephalitogenic strains of herpes virus and the subse- 

 quent demonstration for the same system of "Schienenimmunitat" along 

 neuronal pathways (Hallauer, 1937; Doerr and Kon, 1937; Doerr and 

 Seidenberg, 1937), the possible role of antibody cannot be denied. The time 

 interval between "interfering" and challenge virus was long enough to permit 

 sensitization of the antibody-producing cells by the primary inoculum. 

 Thus, it is conceivable that the challenge dose stimulated a secondary anti- 

 body response of the kind demonstrated in the brain of WEE-vaccinated 

 animals after intracerebral challenge with active WEE virus (Schlesinger, 

 1949). In other words, absence of antibody at the time of challenge inoculation 

 does not necessarily mean that the challenge virus may not itself serve as an 

 antigenic booster dose adequate to ensure effective protection. The possible 

 interplay of interference and specific immune mechanisms is illustrated, for 

 example, by the work of Karzon and Bang (1951) on avirulent (B) and virulent 

 (CG 179) strains of Newcastle disease virus (NDV) in chickens, which suggests 

 a connection between local antigenic booster effect and resistance to the 

 virulent variant. In a previous communication (Bang, 1949), this type of 

 protection had been considered as due to "cell blockade" or interference. 

 Similar relationships may be involved in Gard's (1944) studies on mixed 

 infection with avirulent and virulent strains of Theiler virus. This 

 question has to be settled for each system separately and fortunately 

 does not obscure the situations involving chick embryos or tissue 

 cultures. 



b. "Autointerference"— Its Relation to Heterogeneity of Viral Populations and 

 Genetic Interaction. Autointerference expresses itself in terms of protection or 

 of reduced viral multiplication in hosts inoculated with large doses of a virus 

 which, in smaller doses, is pathogenic and multiplies to high levels. Pasteur's 

 report on rabies in rabbits (1888): ". . . La rage a paru se declarer a la suite 

 d'un quart de seringue plus frequemment que par une ou plusieur seringues 

 ..." states in principle the situation for the following systems: influenza B 

 in chick embryos (Groupe and Pugh, 1950); yellow fever (Smithburn, 1949; 

 Theiler, 1951); dengue (Schlesinger and Frankel, 1952a; Smith, 1956); and 

 RVF (Mims, 1956) in mice; plaque production by egg-adapted influenza 

 strains on chick embryo lung monolayers (Granoff, 1955a); WEE virus in L 

 cells (Chambers, 1957); vesicular stomatitis virus (VSV) in chick embryo 

 monolayers (Cooper, 1958). "Autointerference" obtained with influenza 



