INTERFERENCE 73 



1948), of the allantoic sac (Stone 1948, Schlesinger, to be published), 

 or of tissue culture media (to be published), is proportionately far less 

 effective in blocking the susceptibility of these tissues to infection with 

 active virus. We have also tried to determine whether the interference 

 between influenza and encephalitic viruses (Vilches and Hirst 1947) 

 might possibly be due to the destruction of a common receptor. It was 

 found that (a) W.E.E. virus has no effect at all on the VHI titer of 

 mouse brain extract even on prolonged incubation at 37°C; (b) the 

 VHI titer of brains from mice dead of W.E.E. infection is identical with 

 that of normal brains; (c) W.E.E. virus grows out to full titer in 

 minced embr3^onic tissue even after all demonstrable influenza recep- 

 tors (VHI) have been completely destroyed by receptor destroying 

 enzyme. (To be published. See Schlesinger 1949b.) 



Finally, the demonstration by Henle and Rosenberg (1949) that 

 multiplication of active Lee or PR8 virus can be completely inhibited 

 by intra-allantoic inoculation, during the constant period, of large doses 

 of homologous irradiated virus, also points away from the "receptor- 

 block" hypothesis. In this case, the interfering virus exerts its effect 

 even after the adsorption phase of the infectious cycle is past, the sud- 

 den access of large amounts of inactive virus to already infected cells 

 interrupting the completion of the generative cycle wdthin the cell. This 

 observation more than any other supports the view that the irradiated 

 virus, through the force of its mass, blocks or competes with the infect- 

 ing virus for some cellular component (s?) essential not to the invasion 

 by infecting particles, but to the completion of new infectious par- 

 ticles*. At what point this competition is effective is unknown. We do 

 know from the work of Hoyle (1948) and Henle and Henle (1949) 

 that the emergence of newly formed, fully infectious virus in the allan- 

 toic membrane is preceded by an increase in complement-fixing antigen 

 and hemagglutinin. The effectiveness of homologous irradiated virus 

 is greatest within the first hour after infection and then decreases pro- 

 gressively up to the end of the second third of the constant period. 

 This suggests that inhibition of further viral development may occur 

 at any stage of the intracellular cycle except that in which an increase 

 in complete particles becomes detectable. 



The suggestion that irradiated virus retains the capacity of exerting 

 a specific effect within the cell, or at least at a step beyond the virus- 

 receptor combination, is particularly intriguing because inoculation, 



*It is of interest that the ability of capsular polysaccharides of Friedlander bacil- 

 lus type B to inhibit the multiplication of mumps virus is believed to be due to block- 

 ing of some intracellular metabolic step, but not of the cellular receptors (Ginsberg, 

 Goebel and Horsfall, 1948). 



