INHIBITION OF MULTIPLICATION 201 



extracellular. Similarly, /3-ethoxy-a-ketobutyraldehyde hydrate (Kethoxal) 

 appears to have a direct virucidal action on a variety of animal viruses, i.e., 

 influenza, Newcastle disease, mumps, and vaccinia (McLimans et ah, 1957). 



C. Alteration of Host Cells 



There is some evidence that infection can be prevented or retarded by 

 appropriate alteration of the host cell. Among animal viruses most of the 

 studies directed toward this possibility have been done with influenza. This 

 virus has been used because of the information which has been accumulated 

 regarding the so-called virus receptor of the host cell (Burnet, 1955; Tolmach, 

 1957). 



Treatment with receptor-destroying enzyme derived from Vibrio cholerae 

 (Burnet et al., 1946), has been shown to alter susceptible cells in the allantoic 

 sac of the chick embryo (Stone, 1948a); in the mouse lung (Stone, 1948b); and 

 in the mouse brain (Cairns, 1951). The host cell alteration produced by the 

 enzyme leads to a significant degree of prevention of infection when appro- 

 priate strains and inocula of influenza virus are employed (Burnet, 1955). 

 It appears that the enzyme does alter the receptors of the host cell, for it has 

 been demonstrated that after treatment in vivo, the excised mouse lung shows 

 a reduced capacity to adsorb the virus (Fazekas de St. Groth, 1948a). The 

 receptors apparently are not permanently destroyed, regardless of the extent 

 of treatment with the enzyme, and are capable of regeneration some hours 

 after its removal (Fazekas de St. Groth, 1948b). 



Certain amino-sulfonic acids (Ackermann, 1952), particularly a-amino-^- 

 methoxyphenylmethanesulfonic acid (Ackermann and Maassab, 1954a,b), 

 may also alter host cells and prevent infection with influenza virus. These 

 compounds do not inactivate the virus and do not affect cell respiration in 

 tissue culture. The compound identified above appears to affect an early 

 stage in the process of infection and possibly prevents penetration. It has 

 apparently no effect on the intracellular multiplication process per se, although 

 it appears to affect the release of mature virus particles from the infected cell. 



Numerous other substances have been considered as having some effect on 

 host cells that modifies their capacity to be infected by animal viruses. 

 Comments on these substances are found in the recent reviews by Matthews 

 and Smith (1955) and Hurst and Hull (1956). In the large majority of 

 instances there is not sufficient information to make possible a reasonable 

 decision on the mode or site of action. 



III. Inhibition of Intracellular Multiplication 



The preliminary steps in the initiation of infection by viruses have as their 

 goal the development of a unique biological entity, the virus-infected cell. 

 Attachment of virus particles to host cells and penetration of the virus or its 



