176 R. W. SCHLESINGER 



and monochromatic UV-radiation. The active site responsible for interference 

 appears to reside in a minute fraction of the viral particle (2 X 10 6 A 3 

 volume, mol. wt. 1.6 X 10 6 ). The action spectrum of UV-inactivation 

 suggests that the active moiety is protein in nature, and Powell and Setlow 

 feel that it might be associated with viral RNA but that a possible role of 

 lipids cannot be ruled out. 



Until very recently, all experimental evidence pointed to the inseparable 

 identity of the interfering agent with the physical entity of the inactivated 

 viral particle (Henle and Henle, 1945b; Ziegler et al., 1944; Isaacs and Edney, 

 1950a; Fazekas de St. Groth and Edney, 1952). Paucker and Henle (1958) 

 have found that neither the HA component nor the S antigen obtained from 

 elementary bodies by treatment with ether have any interfering capacity. 

 The possible role of a nonviral macromolecular material ("interferon") 

 liberated by allantoic cells after interaction with inactivated virus (Isaacs et 

 al., 1957; Isaacs and Lindenmann, 1957; Lindenmann et al., 1957) and 

 capable of passively transmitting refractoriness to uninfected cells will be 

 discussed below. 



a. Heterologous Systems. The original observations by Ziegler et al., (1944) 

 and the Henles (1944b, 1945a) were compatible with the view that exposure 

 of the allantois to UV -virus at concentrations sufficient to ensure "infection" 

 of each cell resulted in complete immediate blockade of the cells to super- 

 infecting, heterologous active virus. Fazekas de St. Groth and Edney (1952) 

 calculated that a single particle of inactive virus per cell completely prevented 

 the multiplication in that cell of active heterologous virus added after an 

 interval of 24 hours. Subsequently, Fazekas de St. Groth and associates 

 (1952) demonstrated that in eggs inoculated first with a large dose of heated 

 LEE and 24 hours later with 100 ID 50 of MEL the latter multiplied, but at a 

 rate much lower than in control eggs. Nevertheless, the final titer which the 

 virus attained after about 50 hours was only 1.15 log 10 units lower than the 

 maximum yield in control eggs reached at about 30 hours. When the interval 

 between the two inocula was shortened to 45 minutes, the growth rate of MEL 

 was initially as in control eggs. It changed from the fifteenth hour onward 

 (after about two cycles) to the same slope and ended at the same final yield 

 as in the 24-hour series. It was concluded that interference was not established 

 during the first few hours after inoculation of heated virus. In the light of the 

 important observation of Finter et al. (1954) that allantoic cells, once infected, 

 continue liberating virus at a constant rate for some 36 hours, the data of 

 Fazekas de St. Groth et al. indicate that a proportion of cells (about 7 %) 

 escaped interference even after 24 hours and liberated virus in normal 

 fashion. Along similar lines, Henle and Paucker (1958) found that saturating 

 doses of interfering virus led to complete interference after 9 to more than 24 

 hours, depending on the multiplicity of adsorption of inactive virus. Up to this 



