202 F. L. HORSFALL, JR. 



functional part into the host cell do not in themselves result in infection. This 

 develops only if the virus multiplies — a point of view that has been emphasized 

 recently (Horsfall and Tamm, 1957; Horsfall, 1958). If the virus is to multiply 

 or reproduce, the metabolism of the infected host cell must be altered and 

 redirected so that certain of the products of cell biosyntheses are different 

 from those of the noninfected cell. 



The virus-infected cell is unique because it produces new virus particles; 

 these contain components which are not found in and presumably are not 

 produced by the noninfected cell. In the absence of contrary evidence, it can 

 be assumed that the unusual and new orientation of some of the biosynthetic 

 processes of the virus-infected cell is initiated by the virus particle or a part 

 of it. Recent studies on the metabolism of bacteria infected with bacterial 

 viruses (Putman, 1953; Cohen, 1955; Hershey, 1957) and on the mechanism 

 by which infection is initiated with these viruses (Hershey, 1957) provide 

 strong support for this view, if it be accepted that there are unifying principles 

 in biology, and that one such principle concerns the mechanism of multi- 

 plication of viruses regardless of the nature of their hosts. 



To inhibit intracellular multiplication of viruses it is necessary to affect 

 biosynthetic processes in the virus-infected cell so that new virus particles are 

 not produced in the expected yield. The objective is to prevent, retard, or 

 diminish the effective use of those intracellular processes which are newly 

 oriented in the direction of producing virus precursor materials. It should be 

 emphasized that their potentiality to become so oriented is not discoverable 

 until the cell has become infected. After the virus particle or a part of it has 

 penetrated the cell, but not before, this dormant capability becomes evident, 

 as is proved by the later appearance of new virus particles. 



It is now commonly accepted by workers in the virus field that the bio- 

 synthesis of virus precursor materials in the infected cell occurs largely, if not 

 exclusively, during the so-called latent period. This concept has received 

 largest support and most extensive documentation from studies with bacterial 

 viruses (Putnam, 1953; Cohen, 1955; Hershey, 1957), but there is evidence 

 which points in the same direction with animal viruses (Horsfall and Tamm, 

 1957; Horsfall, 1958). If substances with inhibitory activity are effective 

 because they diminish the production of virus precursor materials, such 

 substances should show activity during the latent period. Relatively few 

 substances have been studied with sufficient attention to the kinetic aspects of 

 multiplication to make it feasible to decide at what step in the process they 

 are active. Those which appear to affect processes occurring during the latent 

 period are discussed below. 



A. Inhibition during Latent Period 

 No more than seven substances have been conclusively demonstrated to 

 inhibit multiplication during the latent period of animal viruses. These are: 



