INTERFERENCE 69 



they are not available in any state resembling pure culture. Even a 

 fairly homogeneous, single-type cell surface structure like the endo- 

 thelium of the chorioallantoic membrane cannot readily be separated 

 from other structures making up the various layers of the membrane. 

 Each cell lives in anatomical and physiological dependence on others 

 and not as an individual entity. Hence, it is impossible, with any 

 degree of assurance, to separate extracellular from intracellular phases 

 of infection. 



(c) The conjecture that interfering viruses have in common an 

 affinity for the same type of cell has in many cases little experimental 

 basis. Histopathological lesions found in infected organs and resulting 

 functional impairments may well be end- or by-products of the infec- 

 tious process, and it is conceivable that the cells involved in the mecha- 

 nism of interference may show no abnormalities at all. 



Bearing these reservations in mind, we have no choice, in view of 

 the intimate association between virus and host cells, but to assume 

 that it is the known or unknown susceptible cell which is the common 

 denominator between the interfering and the interfered-with virus. We 

 have to make this assumption for a relatively simple host organ, such 

 as the entodermal epithelium of the allantoic membrane, as well as for 

 a complex mammalian organ like the mouse brain which contains such 

 a variety of cellular elements other than neurons. The quantitative 

 aspects of interference are in keeping with the assumption that it is 

 effected in conjunction wdth the individual host cell. Thus, while active 

 influenza viruses of types A and B are capable of mutual interference 

 in the allantoic sac of chick embryos under certain conditions of dosage 

 and timing (Ziegler and Horsfall, 1944), it is also possible to propagate 

 a mixture of both serially from egg to egg if the inoculum is properly 

 diluted and adjusted so as to contain comparable amounts of both vi- 

 ruses (Sugg and Magill, 1948). The significance of this latter obser- 

 vation, insofar as it might seem to conflict with the observed interference 

 between the two viruses, would depend on the unequivocal demon- 

 stration that both multiply in the same individual cell. That has not 

 been shown either for this combination or for the mumps- or PVM- 

 influenza combinations for which dual infections in eggs or mice have 

 been demonstrated under some conditions (Gingsberg and Horsfall, 

 1949), while under others, mumps and influenza viruses have given 

 reciprocal interference (mentioned by Henle, W., 1950)- The only 

 convincing instances of simultaneous infection of single cells by two 

 unrelated animal viruses so far recorded appear to be those in which 

 such cells showed both intranuclear and intracytoplasmic inclusion 



