170 R. W. SCHLESINGER 



influenza virus by double infection of cells with active virus (see below), it 

 might be proposed that sublethal concentrations of the virulent virus con- 

 tained some particles by themselves incapable of initiating fatal infection. If 

 cells infected with such particles were superinfected with partially adapted 

 particles, recombination might lead to emergence of virulent progeny. Such 

 progeny could conceivably overgrow the avirulent component since the latter 

 was given in relatively low concentration. The system under study unfortun- 

 ately did not lend itself to a critical test of this hypothesis. Whatever the 

 mechanism of this strange potentiation, its occurrence may be relevant to 

 that of autointerference itself. In the case of influenza viruses, the idea of 

 intrinsic heterogeneity of viral populations has much experimental support 

 (see Section III, B, 4), and the extent to which interference and genetic 

 interactions are interwoven can be amply documented. In other cases, where 

 virulence or lack of virulence are the only distinguishing markers, it may be 

 impossible to choose between the two alternatives. 



3. Interfering Capacity of Inactivated Viruses 



Some inactivated viruses with which interference of one sort or another has 

 been induced are listed in Table III. The vast amount of work done with 

 inactivated myxoviruses will be taken up in detail in Section III, B. The 

 other systems listed have contributed little to our basic understanding of 

 interference other than by confirming that infectiousness, i.e., demonstrable 

 ability to multiply, is not a prerequisite in all systems. 



4. The Role of Timing and Dosage 



Aside from the work with myxoviruses in eggs and tissue culture (see below) , 

 relatively few systems have been subjected to careful quantitative analysis. 

 In all systems utilizing inactivated viruses as interfering agents, their 

 effectiveness depends on administration of saturating amounts. When active 

 virus is used, the amount needed to induce interference varies with its 

 capacity to multiply in the host system and on its rate of multiplication 

 relative to that of the suppressed virus. A good example illustrating these 

 points is the interference by egg-adapted influenza strains with WEE virus 

 in brains of mice (Vilches and Hirst, 1947). When the two viruses were given 

 simultaneously, interference was induced by 10 4 * 9 but not by 10 4,2 EID 50 of 

 the WS strain, and the amount of WEE virus required to overcome this effect 

 increased with greater concentration of WS virus. The infectious titer of the 

 interfering agent in mouse brain dropped progressively from the time of 

 inoculation until none was recovered after 5 days. Despite this limited activity 

 of the interfering virus, interference by large doses was demonstrable for up 

 to 15 days, though decreasing in effectiveness from the seventh day on. 

 Several points of interest emerge from Vilches and Hirst's study: (a) the 



