332 H. B. ANDERVONT 



suggested that the increased proliferative capacity of the cell in which the 

 virus was enclosed provided an environment conducive to the emergence of a 

 variant virus capable of initiating the neoplastic transformation. This 

 variant was not destroyed by the host's antibodies because of its protected 

 position in the cell, but was limited to the transformed cell and its descendants. 

 As time passed, this concept of a masked virus became of major importance 

 to the tumor virus problem and has been invoked to explain unsuccessful 

 attempts to expose viruses as causative agents of tumors. It has become more 

 popular during recent years, following the discovery that some viruses, after 

 gaining access to cells, enter into a vegetative stage where they are not 

 detectable, but later may reappear in the infective stage, which represents 

 the recognizable and familiar virus particle. Noyes and Mellors (1957) have 

 interpreted their recent findings with the papilloma virus as being in accord 

 with this theory. They applied the techniques of immunology and fluorescence 

 microscopy to ascertain the cellular localization of the papilloma virus in 

 lesions from naturally infected cottontails and from laboratory-infected 

 domestic rabbits. In cottontails, the virus w T as found only in the nuclei of 

 epidermal cells and in highest concentration within differentiating cells. It 

 was not found in the layer of deep germinal cells, was abundant in the 

 intermediate keratohyaline layer, and present in lesser amounts in the 

 superficial keratinized layer. In lesions of domestic rabbits only minute 

 amounts of virus were discernible. These findings were consistent with the 

 known characteristics of the virus in these hosts. The investigators suggested 

 that their techniques may have revealed only the complete, or infective 

 stage, virus; it was not found in the deeper proliferative cells because, within 

 them, it may have existed in the incomplete, or vegetative stage, during 

 which it was nonantigenic and, therefore, not demonstrable with the technique. 

 The assumption of a lasting relationship between an inapparent virus and 

 a cancer cell is provocative and should stimulate investigators to explore the 

 mechanisms of this cell- virus relationship. An alternative assumption 

 becomes available for investigation when it is assumed that a virus may be 

 responsible for the change to malignancy but not be essential for the contin- 

 uous proliferative power of the cell. The papilloma virus, according to this 

 postulate, induces primary lesions in the epidermal cells of both cottontails 

 and domestic rabbits, but it reproduces more in its natural cottontail hosts. 

 The appearance of malignancy is not, therefore, correlated with virus 

 multiplication because in the cottontails more papillomas regress and fewer 

 malignancies arise. The transformation to the neoplastic state could represent 

 a chance distribution of susceptible cells among the basal cells of the epidermis 

 and the enduring qualities of the papillomas in domestic rabbits makes their 

 cells more prone to modification. Briefly, differences between the genetic 

 compositions of the cells of cottontail and domestic rabbits are responsible 



