INTERFERENCE BETWEEN ANIMAL VIRUSES 161 



itself. Until more is known about mechanisms of infection with single viruses, 

 there is little hope of understanding the basis of interference. Nevertheless, in 

 a purely technical sense, beginnings have been made in quantitative analysis 

 of the following questions: (a) What is the least amount of interfering virus 

 needed per cell? (b) How rapidly is interference established and how long 

 does it last? (c) Is interference an all-or-none phenomenon, i.e., is an 

 "interfered" cell entirely incapable of being superinfected or can the blocking 

 effect be overcome? (d) Is partial interference due to incomplete inhibition of 

 viral multiplication in all cells of a population or to reduced numbers of 

 virus yielders? Most of the answers — as far as they go — have come from work 

 on myxoviruses in the allantoic membrane and in tissue culture. They will be 

 discussed in the appropriate sections of this chapter. 



III. Experimental Systems 



A. Demonstration of Interference in Mammalian and Avian Hosts 



1. Heterologous Viruses 



The broad spectrum of heterologous viral pairs and host systems with 

 which interference of one sort or another has been demonstrated can best be 

 appreciated by reviewing a summary, such as presented in Table I. Although 

 most of our knowledge concerning quantitative aspects is derived from work 

 on myxoviruses in chick embryos (see Section III, B) or on model systems in 

 tissue cultures (see Section III, C), it would be misleading to disregard the 

 mass of data available from studies in more complex hosts. It is here that the 

 possible scope of the phenomenon will ultimately be related to the natural 

 history of viral infections. 



a. Criteria. The criteria used by different authors or by us in interpreting 

 experimental findings as interference vary in reliability and rigidity. For 

 critical analysis, it would be nice if one could limit discussion to instances 

 which have been subjected to careful quantitation of multiplication inhibition. 

 This cannot be, because much important information, especially about 

 timing and dosage factors, has been obtained from studies in which inter- 

 ference manifested itself chiefly as protection against the pathological con- 

 sequences of the challenge (suppressed) virus. The nature of such protection 

 obviously depends on the host system, and may be against death or disease in 

 animals, lesions, or cytopathogenic effects in tissue culture. It may be partial 

 or complete, just as is inhibition of multiplication. Another criterion is the 

 mutual suppression of immunogenicity found when two or more attenuated 

 viruses are inoculated together (dengue-yellow fever). Of dubious validity 

 is the gradual loss of one of a pair of viruses in the course of serial passages 



vol. in — 11 



