182 R. W. SCHLESINGER 



hundreds of generations. Throughout these manipulations, the cells were 

 resistant to the killing effect of active NDV. Seeding such resistant cells on 

 X-irradiated feeder layers caused massive destruction of both carrier cells 

 and feeder cells. According to G. Henle et al. (1958), MCN or Lung-To cells 

 persistently infected with NDV or mumps virus can be obtained and grown 

 easily and at will. Such cell cultures yield about one infectious unit per 100 

 cells, suggesting either that only an occasional cell is producing virus or that 

 all cells produce virus at an exceedingly slow rate. In favour of the latter 

 hypothesis are two facts: (a) that nearly all cells are relatively resistant to 

 reinfection with VSV, (b) that the "carrier" cultures exhibit a higher rate of 

 aerobic glycolysis than uninfected cells (Green et al., 1958). When VSV- 

 challenged "carrier" cells are incubated for prolonged periods of time with 

 proper refeeding at intervals, the challenge virus eventually (after 12 to 18 

 days) "breaks through" and multiplies to titers nearly equivalent to that 

 obtained in control cultures (Bergs it ah, 1958). This observation indicates 

 that VSV is not initially prevented from combining with the cells. Along 

 similar lines, the resistance of L cells persistently infected with WEE virus 

 to homologous superinfection (Chambers, 1957) and Ackermann's findings 

 on HeLa cells with poliovirus (Ackermann and Kurtz, 1955) should be 

 mentioned. 



This approach, especially combined with the application of plaque assay 

 methods for quantitative analysis, is in its infancy and undoubtedly will be 

 pursued vigorously in the immediate future. It is an exciting prospect, for 

 from studies of this sort we should learn much about the dynamics and the 

 mechanism of interference. The stage is set for the analysis of events taking 

 place in the single "interfered" cell. At the same time, interference here is a 

 most valuable tool for the recognition of latent or persistent association of 

 animal viruses with their host cells. How the knowledge of persistent infection 

 of tissue culture may bear on our ideas concerning broader implications of 

 interference is discussed above (see Section III, A, 1, b). 



IV. Dynamics of Interference — Summary 



Criteria for a rational approach to a comprehensive definition of inter- 

 ference are presented in the introductory section. Of all the experimental 

 systems reviewed, only those utilizing myxo viruses as interfering agents 

 have been analyzed sufficiently to offer some clues to their validity. 



A. Qualitative Criteria — Specificity of Induction 



The basic assumption is that interference is the expression of a specific 

 change brought about by the association of susceptible cells with a virus. 

 What is the experimental support for this assumption? Only the viral 



