198 F. L. HORSFALL, JR. 



in individual virus-infected cells. Because animal virus multiplication, like 

 that of bacterial viruses, is a process that is wholly completed within the 

 individual, infected host cell, inhibition of multiplication needs to be examined 

 at the cell level. 



II. Prevention of Virus Infection 



Infection can be considered to have begun when the infecting virus particle 

 or a part of it has penetrated into a host cell that can support multiplication. 

 To prevent infection it is necessary to alter the extracellular environment, the 

 virus particle, or the host cell so that one or more of the steps leading to 

 penetration do not occur. If infection of all susceptible cells is prevented, no 

 multiplication occurs and no new virus particles are produced. If infection is 

 not completely prevented, a variable fraction of the susceptible cells supports 

 multiplication, and new virus particles appear in a yield that is smaller than 

 that expected in relation to the total population of susceptible cells. The 

 numerical result is identical to that secured when intracellular multiplication 

 is partially inhibited but not entirely blocked. 



On theoretical grounds it should be possible to prevent infection by: (1) 

 altering the extracellular environment so that attachment of virus particle to 

 susceptible cell will not occur; (2) inactivating the infective property of the 

 extracellular virus particle; (3) altering the host cell so that either attachment 

 of the virus particle or penetration of its functional part does not occur. 



A. Alteration of Extracellular Environment 



To prevent infection by alteration of the extracellular environment is 

 relatively difficult in the intact animal, but is readily accomplished with 

 certain animal viruses in tissue culture. As with bacterial viruses, it appears 

 probable that the initial bond formed in attachment of animal viruses to cells 

 is electrostatic in nature (Tolmach, 1957). It would be expected that such a 

 bond would exhibit salt dependence and would show reversibility. A sufficient 

 decrease in the electrolyte concentration of the extracellular environment has 

 been shown to prevent attachment of influenza virus or pneumonia virus of 

 mice to erythrocytes (Davenport and Horsfall, 1948). Similarly, pneumonia 

 virus of mice (Davenport and Horsfall, 1950) and Newcastle disease virus 

 (Levine and Sagik, 1956) are prevented from attaching to host cells if the 

 salt concentration is adequately reduced. The nature of the ionic environment, 

 particularly the type and concentration of cations, also is important for 

 attachment (Burnet, 1952). Although binding to host cells is independent of 

 pH over a wide range, with Newcastle disease virus it is inhibited at pH 4 or 

 10.5 (Levine and Sagik, 1956). It needs to be emphasized that in all instances 



