160 R. W. SCHLESINGER 



Studies along these lines confirm that viral multiplication and production 

 of injury may be dissociated processes (Davenport, 1952). The protective 

 effects of bacterial products are reminiscent of interference-like phenomena 

 encountered in nonviral infections of vertebrates and invertebrates. Indeed, 

 some of these are associated with markedly inhibited proliferation of the test 

 pathogen. Thus, Parry (1956) found that inoculation of 10 3 organisms of a 

 virulent strain of Pasteurella pestis killed mice more rapidly than did 10 6 

 organisms. He also showed that admixture of 10 7 avirulent organisms to 10 3 

 virulent ones gave complete protection, and that India ink had a similarly 

 protective effect. Henderson et al. (1956) found that pre-existing respiratory 

 infection with pathogens, such as Brucella suis or Mycobacterium tuberculosis 

 protected guinea pigs against a different secondary invader given by the 

 respiratory route. The phenomenon seemed to depend on the ability of both 

 organisms to spread via the lymphatic system. If the latter was circumvented, 

 no protection was observed. 



Although the older and recent literature abounds with such reports, 

 amazingly little is known about underlying mechanisms. Usually some 

 alterations in the host's systemic defense apparatus are postulated which may 

 involve phagocytes, the properdin system, or stimulation of certain enzymes 

 (cf. report by Rowley (1956) on lipopolysaccharide-splitting phosphatase 

 produced by animals injected with bacterial lipopolysaccharides). Undoubted- 

 ly, similar systemic effects can modify the response to pathogenic viruses and 

 may be at the root of some of the observations referred to above. Be that as it 

 may, the superficial resemblance of results like those of Parry and Henderson 

 to autointerference and homologous or heterologous interference among 

 viruses is sufficiently confusing to impose the need for restrictive criteria. 

 In the qualitative sense, it is postulated that interference results uniquely and 

 directly from an association of the interfering virus with susceptible cells, and 

 that this association is primarily responsible for the inability of the superinfecting 

 virus to multiply and to cause cell injury. This restriction does not invalidate 

 the possibility, suggested by recent experimental evidence (Isaacs et al., 1957; 

 Isaacs and Lindenmann, 1957), that infected cells may release specific 

 reaction products which, though not identifiable as virus in nature, may 

 "transmit" interference to noninfected cells. 



B. Criteria for Quantitative Analysis 



The key to an understanding of the meaning and the mechanisms of 

 interference lies in the fate of the interfering virus, of the suppressed virus, 

 and in the specific changes induced in the infected cells by the interfering 

 virus. Technically, interference is a manifestation of mixed infection of cells. 

 This circumstance compounds the difficulties encountered in developing 

 fruitful experimental approaches to the elucidation of the infectious process 



