INTERFERENCE 75 



influenza types A and B, the situation involving viruses as dissimilar 

 as influenza and W.E.E. appears even more confusing. At least it is 

 clear from the results already mentioned that these viruses do not have 

 common cellular receptors. The alternative explanation, i.e. common 

 intra-cellular elements involved in the infectious process, has received 

 some experimental support in recent observations in our laboratory. It 

 had been found previously (Henle and Henle 1946, Vilches and Hirst 

 1947) that non-neurotropic strains of influenza virus, despite their 

 "toxicity" and their interfering effect after intracerebral inoculation into 

 mice, did not multiply in the mouse brain. Measurements of hemag- 

 glutination-inhibitor (receptor) titers of extracts from mouse brains 

 harvested following intracerebral inoculation of the PR8, WS or Lee 

 strains revealed progressive reduction in VHI with subsequent return 

 to normal values (Schlesinger 1949b). The VHI decrease was of low 

 order of magnitude when compared with that associated with infection 

 with the neurotropic variant of the WS strain, but it was of the same 

 order as that found in mouse lung extracts obtained from mice in the 

 course of fatal infection with PR8 virus. This receptor decrease sug- 

 gested some viral activity which was not in line with the observed 

 decrease in infectious titer. It has now been possible to show that intra- 

 cerebral inoculation of PR8-, WS-, or Lee-infected allantoic fluids in 

 large amounts leads to the production, in mouse brain, of "incomplete" 

 virus (hemagglutinin and complement-fixing antigen) in the face of 

 progressive decrease in infective titer (Schlesinger 1950, details to be 

 published). The production of hemagglutinin appears to be limited 

 to a period corresponding to a single cycle of virus multiplication in 

 the allantoic membrane. The maximum yield reached at the end of 

 this period varies in direct proportion to the amount inoculated. This 

 observation makes it plain that certain cells which are incapable of 

 supporting the complete self-reproduction of these virus strains, never- 

 theless, allow the virus to undergo some phases of viral growth which, 

 in fully susceptible cells, seem to precede the completion of the infec- 

 tious particles. If the intracerebral inoculum is heavy enough, i.e. if 

 a large number of cells in the brains are involved in this process, they 

 are sufficiently impaired to lead to "toxic" death after 1 to 2 days. It 

 appears reasonable to assume that it is these cells which are involved 

 also in the infection with W.E.E. virus and with other neurotropic 

 viruses with which influenza strains interfere. The necessity of using 

 large doses of influenza virus to obtain significant degrees of interfer- 

 ence is undoubtedly related to the necessity to infect many cells simul- 

 taneously because of the limitation of its incomplete growth to a single 

 cycle. 



In the light of the last mentioned and all the other recently accu- 



