INTERFERENCE BETWEEN ANIMAL VIRUSES 177 



time, the yield of newly produced virus was directly proportional to the 

 amount of challenge virus inoculated but gradually decreasing with increasing 

 time intervals. The fact that these authors, in contrast to Fazekas de St. 

 Groth, obtained no evidence suggesting that some cells escaped the interfer- 

 ing effect altogether may be due to the greater efficiency of UV-irradiated as 

 compared with heated virus (Henle, personal comment). 



It can be concluded that (a) a single inactivated viral particle can induce 

 interference in a cell; (b) establishment of complete inhibition requires about 

 16 to 24 hours of contact between inactivated virus and cell; (c) a proportion 

 of exposed cells may escape the interfering effect of the inactivated virus; (d) 

 the yield of new virus from "interfered" cells decreases progressively until 

 complete inhibition is established. 



b. Homologous Systems. The marked depressing effect of inactivated 

 influenza virus on the yield of superinfecting, homologous, active virus was 

 demonstrated by Henle and Henle (1943, 1944a,b), Ziegler et al. (1944), and 

 Isaacs and Edney (1950, 1951). They showed that inoculation of heat-or 

 UV-inactivated virus in high concentration resulted in relatively low yields 

 in terms of both infectious and HA titers. The conditions under which these 

 observations were made closely paralleled those already described for 

 heterologous interference. The first inkling of a fundamental difference 

 between homologous and heterologous interference came with the discovery 

 by Henle et al. (1947b) and Henle and Rosenberg (1949) of the effect of 

 UV-irradiated virus inoculated after infection with active virus. They found 

 that heterologous UV-virus did not affect multiplication in already infected 

 cells; it did, however, block previously uninfected cells and thus viral 

 multiplication was limited to a single step. Homologous UV-virus, in contrast, 

 blocked not only uninfected cells but also suppressed production of infectious 

 virus in the cells infected by the primary inoculum. The completeness of this 

 block depended upon (a) the time interval (complete at 1 hour, decreasing 

 progressively to the sixth hour), (b) the dosage. Active PR8 was effectively 

 inhibited by inactive PR8, MEL, WS, and partially by Swine. The contrast 

 here between homologous and heterologous pairs suggested that a cell 

 already engaged in synthesis of viral material could still accept additional 

 homologous virus. These earlier results of Henle et al. were based on infectivity 

 titrations of the progeny only. Later findings (Liu et al., 1956) suggested that 

 superinfection with homologous, irradiated virus may actually result in the 

 production of "incomplete" virus rather than in total suppression of viral 

 replication. 



When inactive and active homologous virus are inoculated either simul- 

 taneously or consecutively in the order named, additional evidence for 

 multiple infection of single cells is obtained. Henle and Liu (1951) reported 

 that multiplicity reactivation occurred in eggs inoculated with large doses of 



VOL. Ill — 12 



