186 R. W. SCHLESINGER 



or heterologous myxoviruses must differ from that by which the same virus 

 inhibits multiplication, say, of equine encephalitis virus. What are the 

 differences? What is the residual biological activity of an "inactivated" virus 

 particle that can have such a profound effect on the cell's response to super- 

 infecting virus? What possible justification — other than our ignorance about 

 mechanisms — can there be for classifying together under a single term two 

 phenomena as manifestly different as the resistance to EE virus of mice 

 infected with Theiler virus and the refractoriness to superinfection of single 

 cells in a clone persistently infected with NDV? Are some of the phenomena 

 which we call interference simply due to the destruction of susceptible cells by 

 one of two pathogenic viruses, cf. TO- WEE, while at the other extreme we are 

 dealing with relationships as intimate as lysogeny in phage-infected bacteria? 



Even in the case of bacterial viruses, basic mechanisms involved in inter- 

 ference remain unsolved. It has been possible, however, to differentiate some 

 expressions of mixed or multiple infection by descriptive terms with specific 

 connotations. Mutual exclusion is the resistance of infected cells to super- 

 infection with a related or unrelated virus; the depressor effect is the lowering 

 of the yield of the first infection by the superinfecting and excluded phage; 

 immunity of lysogenic bacteria to superinfection follows laws of specificity 

 differing from those governing mutual exclusion between virulent phages. 

 Techniques are available by which these phenomena can be differentiated 

 from reactivation or genetic recombination or phenotypic mixing. Never- 

 theless, making these distinctions will be greatly complicated if, for example, 

 it should ever prove that one viral mutant has a distinct selective advantage 

 over another one; or, if mixed infection with N related phages, each having 

 distinct genetic markers, should reveal that fewer than N particles can 

 participate in the production of progeny in a single infected cell. Despite such 

 theoretical reservations, it is clear even now that in multiple or mixed infection 

 of bacteria a variety of yield-limiting mechanisms may operate whose 

 recognition has given rise to a usable descriptive terminology. 



The fact that, in the case of animal viruses, we lump together so many 

 diverse phenomena under the single heading of "interference" merely attests 

 to the lack of basic information necessary for a more discriminating termino- 

 logy. In a purely descriptive sense, one is tempted to see analogies to mutual 

 exclusion, depressor effects, or lysogeny, and to add to these a number of 

 other hypotheses. At this time, however, there is little solid experimental 

 support for any definitive differentiation. What little evidence there is, has 

 been derived either directly or indirectly from studies on adsorption and 

 penetration of interfering or suppressed myxoviruses. 



A. Nature of Association of Interfering Virus and Cell 

 Inactivated, interfering influenza virus is adsorbed and "disappears" in the 

 allantoic membrane much as active virus does (Henle and Henle, 1944b; 



