74 SCHLESINGER 



during the constant period, of irradiated heterologous virus fails to in- 

 hibit the completion of the growth cycle (Henle and Rosenberg 1949). 

 This suggests that, in contrast to the homologous, the heterologous 

 virus is not capable of invading cells already infected with the active 

 virus and hence not in a position to block its complete cycle of repro- 

 duction. The analogy between this speculation and observations on 

 phages is obvious: here the active virus already in the cell is no ob- 

 stacle to the subsequent entrance of homologous particles, but it ex- 

 cludes the particles of the heterologous type ("mutual exclusion") . This 

 is in good agreement with the fact that irradiated virus is equally 

 effective in interfering with either homologous or heterologous active 

 virus if inoculated before or simultaneously with the latter. 



It is not unlikely that this blocking effect of homologous UV- 

 inactivated virus may be related to the "auto-interfering" capacity 

 of influenza virus in high concentration. Inoculation into eggs of dilute 

 infected allantoic fluids yields virus of maximal titer. But if the seed 

 consists of undiluted or concentrated allantoic fluid, the yield is lower 

 (Henle and Henle, 1944a). When serial passages from egg to egg are 

 done with undiluted PR8-infected allantoic fluids, the yield of hemag- 

 glutinating virus remains high in each passage with only a slight de- 

 crease, while the infective titer decreases progressively and markedly, 

 especially in the third and fourth passage (von Magnus 1946, Gard 

 and von Magnus 1946, Gard et al., 1947). The non-infective, hemag- 

 glutinating virus is believed to be a "precursor" of the fully developed 

 virus. It is of special interest that continuation of the serial transfers 

 beyond the fourth passage (when both, hemagglutinin and infective 

 titer, are lowest) may lead to a rise in infective titer to maximal values 

 in the fifth and a repetition of the shift thereafter (personal observa- 

 tion). Thus, the qualitative change from the fully developed, self- 

 reproducing virus (sedimentation constant of about 700 S) into a modi- 

 fied form (sedimentation constant said to be about 500 S [Gard et al., 

 1947]) does not — as one might expect — end in the eventual disappear- 

 ance of infectious particles altogether, but, on the contrary, in their 

 sudden resurgence in full strength. The fact that hemagglutinin 

 reaches maximal or almost maximal titers in each passage indicates 

 that whatever interference takes place is not with multiplication of 

 virus but only with its completion. This phenomenon has not as yet 

 been adequately explained. It is important to realize, however, that 

 it occurs only if the passage materials contain virus of either form in 

 high concentration. 



With so much speculation still required to bring order into the prob- 

 lem of interference between viruses as closely related to each other as 



