INTERFERENCE 7I 



Example 3: If active virus is incapable of multiplication, but can in- 

 terfere, large quantities are required which may impair the integrity of 

 cells. — The most striking example in this category is the interference, 

 again in the mouse brain, between non-neurotropic strains of influenza 

 virus and certain neurotropic viruses, e.g. W.E.E. Vilches and Hirst 

 (1947) have shown that relatively large amounts of influenza virus have 

 to be given for significant interference. That influenza virus is not en- 

 tirely innocuous for the mouse brain is clear from Henle's studies on 

 its "toxicity" after intracerebral inoculation of high doses (Henle and 

 Henle, 1946). At least one strain, the W.S. of type A influenza virus 

 is "potentially pathogenic" in that it can be adapted to the mouse brain 

 so that it multiplies there and produces typical encephalitis (Stuart- 

 Harris 1939, Francis 1940). Further pertinent effects of intracerebral 

 inoculation of non-neurotropic influenza viruses have recently been 

 observed in our laboratory, and will be described below in a discussion 

 of the mechanism of interference on the basis of the most amenable 

 study object, i.e., influenza virus. 



Example 4: Inactivated interfering virus retains the ability to im- 

 pair the integrity of the cell, and large quantities are required. — Ultra- 

 violet-irradiated influenza virus of one type, if given in large amounts, 

 can interfere in the egg with the propagation of active virus of another 

 type (Henle and Henle 1943, i944a,b, 1945, Ziegler, Lavin and Hors- 

 fall, 1944). If ultraviolet-irradiated influenza virus is injected in high 

 concentration, it significantly inhibits the growth of the allantoic mem- 

 brane and also of the embryo itself (Henle, Henle and Kirber, 1947). 

 This growth-inhibiting action is ultraviolet-resistant to about the same 

 extent as the ability of the virus to interfere in the egg with active 

 homologous or heterologous influenza virus. The fact that interference 

 by irradiated influenza virus also requires the administration of large 

 amounts again suggests that it is related to its residual abiUty to affect 

 the normal function of the host cell. Similarly, bacteriophage which 

 after irradiation retains its interfering capacity inhibits bacterial multi- 

 plication (Luria and Delbriick, 1942). 



While these examples are chosen arbitrarily from a large number 

 of observations (see Henle 1950), it seems that no instance of inter- 

 ference has been described in the hterature which would contradict in 

 essential points the general suggestions which they serve to illustrate. 



These statements do not say anything specific concerning the mech- 

 anism underlying interference. It may be said without much argu- 

 ment that all evidence points to the virus particle itself, whether active 

 or inactivated, as the essential factor. 



