196 F. L. HORSFALL, JR. 



with viruses, and numerous other variables may alter the process of virus 

 multiplication. As a general rule, the more abnormal the environmental or 

 metabolic conditions, the more marked is the inhibitory effect on multiplica- 

 tion. 



A large number of biological materials and chemical compounds affect the 

 multiplication of animal viruses. The great majority of these substances tend, 

 in widely varying degree, to inhibit the process. A few substances are known 

 to have a different effect and lead to augmentation of multiplication. None of 

 the inhibitory substances presently known has been demonstrated to be 

 useful in the management of naturally occurring virus infections of animals or 

 man. 



The effects of various biological materials and chemical compounds on 

 virus multiplication have been the subject of recent reviews by Matthews and 

 Smith (1955), Horsfall (1955a,b), Hurst and HuU (1956), Tamm (1956a, 1958), 

 Horsfall and Tamm (1957.) No attempt will be made to present a complete 

 evaluation of the properties and capabilities of the large number of inhibitory 

 materials that have been reported. The present discussion is concerned 

 largely with the possibility that principles bearing on inhibition can be 

 discerned and that conceptual schemes erected on such bases may be useful 

 in furthering investigations on the mechanism of virus multiplication. 



The multiplication of animal viruses has been approached in different ways 

 by different workers. Some have not made a sharp distincton between 

 multiplication and its incidental sequelae — lesions and disease. Others have 

 been concerned exclusively with the pathological alterations that sometimes 

 are the end results of multiplication. Relatively few have focused attention 

 closely on the processes which lead to the production of new virus particles in 

 the infected cell. During recent years, ideas that have evolved from the 

 detailed study of the reproduction of bacterial viruses have strongly influenced 

 experimentation and concepts in the animal virus field. Much modern work 

 on the multiplication of animal viruses is similar in plan and objectives to that 

 with bacterial viruses and has led progressively to the view that the mecha- 

 nisms involved have much in common. 



Studies with inhibitory materials have, in many cases, suffered from the 

 failure to make a clear distinction between virus multiplication per se and the 

 effects of the process or its products upon host cells and tissues. In many 

 reports little or no attention has been given to the mechanism of inhibition. 

 In some it has been assumed that, because the incidence of lesions or death of 

 the animal was reduced when a compound was used, multiplication of the 

 virus must also have been inhibited. Such an assumption is unwarranted and 

 may be in error. To determine whether a substance inhibits multiplication it 

 is essential to measure the rate or the extent of multiplication that occurs in 

 its presence and compare this with the results of identical measurements 



