82 SHOPE 



rabbit will also be refractory to reinfection with fresh cottontail papil- 

 loma virus. Another bit of indirect evidence indicating the persistence 

 of papilloma virus in domestic rabbit papillomas is furnished by the 

 observation that a noninfective suspension of domestic rabbit papilloma 

 tissue, if injected subcutaneously or intraperitoneally into another do- 

 mestic rabbit, will render that animal immune to cottontail papilloma 

 virus as indicated by the development of virus neutralizing antibodies 

 in the blood serum and a refractory state to active infection with the 

 virus (2). The evidence therefore is that even though papilloma virus 

 in an infective form is not present in domestic rabbit tumors, it is pres- 

 ent in an occult or "masked" form which is still capable of eliciting the 

 characteristic immune responses of fully infective papilloma virus. 



The mechanism by which papilloma virus is "masked" in the do- 

 mestic rabbit tumors is not known. Some investigators believe that 

 virus-neutralizing antibody constitutes the "masking" agent. This 

 scarcely seems the correct explanation because virus-neutralizing anti- 

 body is present in the serum of infected cottontail rabbits without 

 "masking" of the cottontail papilloma virus. 



Aside from serving as a good example of a "masked" virus, papil- 

 loma virus as it exists in domestic rabbit tumors points to the possibility 

 that this class of agents ("masked" viruses) may have wdde implications 

 in the tumor field in general and may play a large role in that group 

 of mammalian tumors now believed to be nonviral in causation. It is 

 probably farfetched to think that very many apparently spontaneous 

 and noninfectious mammalian tumors have as their cause a virus native 

 to another species, but the case of the papilloma virus indicates that 

 such an eventuality is not beyond the realm of possibility. Less far- 

 fetched is the possibility that, in some tumors in which a carcinogenic 

 virus cannot be demonstrated by any means yet tried, virus "masking" 

 after the manner of the papilloma agent may be responsible for the 

 apparent absence of virus. It seems likely that all of the carcinogenic 

 viruses amenable to conventional techniques of isolation have been 

 brought to light. Yet the very existence in a tumor of an agent like 

 "masked" papilloma virus indicates the possibility that agents more 

 elusive than the conventional tumor viruses may exist and may even 

 be quite common so far as anything we know. The possibility that 

 "masked" papilloma virus may represent the prototype of these more 

 elusive carcinogenic agents makes it especially urgent that we learn as 

 promptly as possible just what constitutes the "masking" process in the 

 case of the papilloma virus. Thus far we do not even have a half prom- 

 ising lead. 



