188 R. W. SCHLESINGER 



Henle, 1951a; Edney and Isaacs, 1950). On the basis of this evidence, Henle 

 (1950) and Isaacs and Edney (1950b,c) postulated that interference in the 

 influenza-influenza system is probably localized at an intracellular site 

 beyond the stage of adsorption. This interpretation is certainly in line with 

 the established close relationship between interference and genetic recombina- 

 tion or reactivation which indicates that pre-emption of a cell by inactivated 

 viral particles does not exclude invasion by active particles. If we could 

 identify the fundamental difference between the conditions enabling an 

 inactivated particle to contribute genetic markers to recombinant progeny 

 and those leading to interference, we would be a good deal closer to an 

 understanding of mechanisms. 



Another system for which experimental evidence strongly points to an 

 intracellular mechanism is that concerned with interference by active 

 myxoviruses with EE virus. Here it was shown by Schlesinger (1951) that the 

 cellular receptors for influenza virus could be effectively destroyed by treat- 

 ment with RDE without affecting susceptibility of tissue fragments to EE 

 virus. More recently, Levine (1958) confirmed this observation by showing 

 that monolayers of chick embryo fibroblasts infected with NDV attached the 

 same number of plaque-forming units of WEE virus as uninfected mono- 

 layers. Levine's quantitative data, already described, suggest that inter- 

 ference in this system may involve direct competition for cellular constituents 

 (or for limited sites?) required for replication of both viruses. The idea of direct 

 mutual competition is in line with the early observation by Vilches and Hirst 

 (1947) that suppression of a slowly multiplying strain of WEE virus was much 

 more effective than that of a rapid mutant. Furthermore, large doses of 

 UV-irradiated (Henle and Henle, 1945a; Vilches and Hirst, 1947) or of 

 "incomplete" influenza virus (Schlesinger, 1951) do not effectively interfere 

 with WEE virus. All these considerations point indeed to mutual intracellular 

 inhibition by two actively multiplying viruses. 



In contrast to the inferred intracellular localization of interference by 

 influenza viruses, Baluda's (1957) evidence concerning the fate of super- 

 infecting NDV or UV-NDV-infected cells again suggests that he is dealing 

 with a surface phenomenon. He has shown that superinfecting particles 

 disappear from "interfered" cells more rapidly than from normal ones. That 

 fraction which remains attached can be inactivated by antibody at a time 

 when virus in association with normal cells would no longer be neutralizable 

 because it has penetrated. Baluda therefore suggests that active NDV, 

 after adsorption on "interfered" cells, is either inactivated at the cellular 

 surface or prevented from penetrating into the cell. Application of 

 isotope techniques may help decide between these alternatives, much 

 as it has in the case of mutual exclusion between phages (French et al., 

 1951). 



