172 R. W. SCHLESINGER 



demonstration of gradual "overcoming of interference" with increasing 

 intervals between the two inoculations; (b) the fact that suppression of a 

 slowly multiplying variant (Lederle) of WEE virus was much more effective 

 than of a rapidly multiplying one (Rockefeller Institute strain). This aspect 

 has gained added significance as a result of studies by Levine (1958), suggest- 

 ing that NDV and WEE virus are mutually competitive in tissue culture 

 (see Section III, C); (c) in keeping with the restricted multiplication of influenza 

 virus in mouse brain (Schlesinger, 1950, 1953; Cairns, 1951, 1954), there was 

 no significant increase in the amount of WEE virus suppressed as the interval 

 between the two inoculations was lengthened from to 7 days. This is 

 contrary to systems in which the interfering virus multiplies and spreads from 

 cell to cell, as exemplified by the inhibition of WEE virus in mice previously 

 inoculated intracerebrally with the TO strain of Theiler virus: the longer the 

 interval between the two inoculations, the greater the resistance to WEE 

 virus (Schlesinger et al., 1943; Schlesinger, 1952). 



Although conclusions based on experiments done on intact animals are in 

 general agreement with the principles governing interference in the allantoic 

 cavity or in tissue culture, they do not lend themselves to truly quantitative 

 interpretations. 



5. Localized Character 



Interference is set apart from systemic immune mechanisms not only by 

 specialized requirements with regard to timing and dosage but also by its 

 localized character. Thus, localization of protection to neuronal pathways 

 traveled by interfering virus was demonstrated by Magrassi (1935) and by 

 Doerr et al. (Doerr and Kon, 1937; Doerr and Seidenberg, 1937) and Hallauer 

 (1937) with herpesvirus, and later by Jordan and Duffy (1952) for hetero- 

 logous pairs, such as SLE and WEE viruses. The work by Sulkin et al. (1953) 

 also suggests that pre-emption of certain levels of the spinal cord of mice by 

 Coxsackie virus may afford local protection against poliovirus. Henle et al. 

 report (1947a) that the amniotic sac of chick embryos whose allantoic 

 membrane is blocked by UV virus retains full susceptibility to active 

 influenza virus. Henle and Henle (1945a) also have shown that inactivated 

 influenza virus protects chick embryos against death due to WEE virus, 

 provided great care is taken to ensure that the latter has primary access only 

 to allantoic cells. When such precautions are not taken, no protection is 

 achieved (Vilches and Hirst, 1947). Similarly, Bang (1949) reports protection 

 by inactivated against active NDV when both are inoculated on the dropped 

 CAM, but not when the active challenge virus is inoculated intra-allantoically. 

 The situations involving protection against lethal effects of myxoviruses are 

 complicated by the possible role of "toxic" factors and by variations in the 

 ease with which different strains spread systemically to the embryo, which 



