200 F. L. HORSFALL, JR. 



reacts with the protein components of the virus particle, not with the 

 separated nucleic acid which carries the functional capacity to initiate 

 reproduction in an appropriate host cell. There are indications that point in the 

 same direction with animal viruses; the separated infective nucleic acid 

 fraction of Mengo virus (Colter el al., 1957) is not inactivated by neutralizing 

 antibody, which does inactivate the infectivity of the intact virus particles. 

 These results raise the possibility that virus particles neutralized by specific 

 antibody may retain the intrinsic capacity to initiate multiplication but are 

 prevented from manifesting it through inability either to bind with host cells 

 or to penetrate the cell membrane. In support of this idea, Isaacs (1948) has 

 demonstrated that anti-influenza virus serum prevents attachment of this 

 virus to erythrocytes. The well-established fact that neutralizing antibody 

 does not alter the kinetics of the intracellular multiplication process after the 

 virus has penetrated the host cell can be taken as confirmatory evidence. 

 The work of Watson and Coons (1954) leaves little doubt that antibody can 

 penetrate host cells, but it is well established (Ginsberg and Horsfall, 1951b) 

 that it does not produce any effect upon the intracellular virus particle or its 

 functional part comparable to that it produces on the intact extracellular 

 virus particle. 



The question whether neutralizing antibody and virus particle can 

 dissociate with apparent reactivation of the infective property seems not to be 

 decisively resolved. Certain studies (Tyrrell and Horsfall, 1953) indicate that 

 reactivation of the infectivity of a neutralized mixture occurs on dilution. 

 Others (Dulbecco et al., 1956) have secured contrary results. It must be 

 emphasized that infectivity is a positive operational concept that has meaning 

 only with respect to particular host cells under specified environmental 

 conditions. Noninfectivity is, in contrast, a negative concept which has 

 meaning only in relation to the conditions specified. The difficulties of a 

 decision regarding noninfectivity produced by neutralizing antibody have 

 been underscored by Tyrrell and Horsfall (1953). 



Many materials have been tested with a view to finding means other than 

 antibody to inactivate extracellular virus particles in vivo. The extraordinary 

 instability of certain animal viruses in vitro; some, i.e., influenza and mumps, 

 have an infective half-life that is no longer than an hour or two 35°C. 

 (Horsfall, 1955c), suggests that their inactivation should be readily achieved. 

 Numerous substances are effective in vitro, and appear to inactivate virus 

 particles directly, but nearly all are so damaging to host cells as to prevent 

 their use in vivo (Horsfall and Tamm, 1957). An exception is provided by 

 synthetic polylysine peptides (Green and Stahmann, 1954), which appear to 

 combine directly with a number of animal viruses, i.e., influenza, mumps, 

 Newcastle disease, and infectious bronchitis, as well as with tobacco mosaic 

 and certain bacterial viruses, and inhibit their infectivity while they are 



