Are Animal Tumor Viruses Always Virus-Like?

Three tumors initiated by well characterized viruses, but in which virus is not detectable by ordinary virological techniques, are discussed. The question of the possible state of the virus within these seemingly non-infectious tumors is considered, largely from the standpoint of findings with the rabbit papilloma virus. This agent in its natural host, the cottontail rabbit, is infective, can be seen as virus bodies with the electron microscope, and can be visualized with fluorescent antibody only in the upper keratinizing cells of individual papillomas. At the growing bases of such papillomas, where neoplasia is in active progress, no infective virus is demonstrable and viral bodies cannot be visualized by either the electron microscope or fluorescent antibody. A hypothesis is presented that rabbit papilloma virus exists in cottontail papillomas in two forms-one, the complete mature virus, composed of nucleic acid and protein, and the other, immature virus, composed of naked viral nucleic acid without its protein coating. The function of the mature papilloma virus is to initiate tumor formation,-that of the immature virus, to maintain neoplasia. In the non-infective domestic rabbit papilloma, the viral nucleic acid and protein fail to combine to form mature infective virus and, as in the cottontail papilloma, neoplasia is maintained by the activity of the viral nucleic acid alone.