INHIBITION OF MULTIPLICATION 199 



it is necessary to produce gross and very unphysiological alterations in the 

 electrolyte environment to prevent attachment. 



In theory, reversal of attachment should also prevent infection. The period 

 during which reversibility is demonstrable may be brief and the phenomenon 

 difficult to demonstrate with animal viruses, but there are indications that it 

 exists. Cation exchange resins (Puck and Sagik, 1953) can reverse the attach- 

 ment of influenza virus to erythrocytes. A sufficient increase in temperature 

 reverses the attachment to cat erythrocytes without causing destruction of 

 cell receptors (Tamm, 1954a). Similarly, reduction in the electrolyte con- 

 centration reverses the attachment of pueumonia virus of mice to host tissue 

 particles or erythrocytes without affecting the combining power of either 

 (Davenport and Horsfall, 1948, 1950). 



B. Inactivation of Extracellular Virus 



Inactivation of the infective property of extracellular virus particles is by 

 far the simplest and the most generally used means for preventing infection of 

 susceptible host cells. Specific neutralizing antibody is the antiviral substance 

 commonly used and is much more effective than any other. In the great major- 

 ity of instances, neutralizing antibody converts infective virus particles into 

 noninfective particles at a rapid rate and with an efficiency that approaches 

 but does not quite reach 100 % (Dulbecco et al., 1956; Rubin, 1957). It appears 

 that a small fraction of particles resists neutralization, but no satisfactory 

 explanation has been provided for this so-called persistent fraction, which 

 was recognized much earlier in studies with bacterial viruses (Andrewes and 

 Elford, 1933; Burnet et al., 1937). Recent studies (Dulbecco et al., 1956; Rubin, 

 1957) have been interpreted as indicating that the persistent unneutralized 

 particles are in no other way demonstrably different from the particles that 

 are neutralized; they appear to have the same antigenic make-up, are not 

 genotypically different, and on multiplication in susceptible cells yield new 

 particles that react with neutralizing antibody to the same extent as did the 

 initial population of virus particles. 



The mechanism by which neutralizing antibody inactivates the infective 

 property of viruses is not known. There are indications that neutralization 

 is a direct result of combination between virus particle and antibody — that 

 the binding of one antibody molecule by a virus particle may cause inactiva- 

 tion (Dulbecco et al., 1956). There is also evidence for the view that antibody 

 inactivates virus particles by preventing penetration of susceptible cells by 

 the agent (Rubin and Franklin, 1957; Rubin, 1957). The kinetics of inactiva- 

 tion in the presence of antibody excess is of first order during the initial phase 

 of the reaction; the rate is directly dependent on the concentration of antibody. 



Recent work with bacterial viruses (Lanni and Lanni, 1953) and with plant 

 viruses (Schramm and Gierer, 1957) indicated that neutralizing antibody 



