70 SCHLESINGER 



bodies characteristic of the two infecting viruses (Anderson, K. 1942, 

 Syverton and Berry, 1947). 



In most examples of interference between animal-pathogenic viruses 

 which have been described in the literature, the interfering agent has 

 the actual or potential abihty to impair the integrity of certain cells 

 in a characteristic manner*. This generaHzation applies regardless of 

 whether the interfering virus is active or "inactivated." In either case, 

 the intensity of the inhibitory effect is proportional to the quantity of 

 interfering virus to which the susceptible tissue is exposed, and may 

 be related to its ability to interact in some specific way with the cells 

 of that tissue. We can test the validity of this broad statement by ex- 

 amining specific instances of interference. 



Example 1: With actively multiplying virus, the interfering capac- 

 ity increases with progression of the infectious process. — This is ex- 

 emplified by the interference, in the mouse brain, between Theiler 

 virus (T.O.) and Western equine encephalitis (W.E.E.) virus, two 

 totally unrelated agents (Schlesinger, OHtsky and Morgan, 1944a). 

 Mice inoculated intracerebrally with 1 00 ID50 of T.O. develop paralysis 

 of the extremities after 9 to 14 days. If they are reinoculated during 

 the incubation period with graded amounts of W.E.E. — which produces 

 fulminating encephalitis with death after 2 to 3 days in control mice — 

 they show a gradually increasing degree of refractoriness to the latter. 

 By the 8th day, they resist as much as 10^ LD50 of W.E.E. The course 

 of the infection with T.O. virus is, however, in no way affected by the 

 intervening inoculation of the more virulent of the two. 



Example 2: With actively multiplying virus, the degree of inter- 

 ference wears off after arrest of the interfering infection. — Vaccination 

 of laboratory animals with formalin-inactivated Western E.E. virus 

 leads to immunity to W.E.E., but not to the immunologically distinct 

 Eastern E.E. virus. However, the specific immunity is not absolute, 

 and intracerebral challenge with W.E.E. may result in an abortive en- 

 cephahtis during which some virus multiplication may take place. This 

 abortive infection renders the animals temporarily refractory to sub- 

 sequent infection with Eastern E.E. or vesicular stomatitis virus. After 

 2 to 3 weeks, full susceptibility to the heterologous agents is restored, 

 while specific immunity persists (Schlesinger, Olitsky and Morgan, 

 I944a,b). 



* In speaking of this ability as "potential," I mean that most "non-pathogenic" 

 interfering viruses have either the inherent capacity of being "adapted" to the host 

 tissue in which they interfere, or are derivatives of parent strains which are patho- 

 genic for that tissue. 



