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Ecotropic C-type retroviruses isolated from both normal and dimethylbenzanthracene-treated DBA/2 mice could be classified into three major groups, Ea, Eb, and Ec, that differed in structure and biology. Weanling DBA/2 mice were generally free of viruses, but a fraction of adult individuals became virus positive and were apparently selectively associated with a high expression of the Eb viruses. Some of the ecotropic viruses from DBA/2 mice acted as exogenous pathogens. They caused viremia and a moderate incidence of leukemia when injected into C3H and ST/a mice. In addition, they caused an appreciable number of early deaths without signs of malignancy. To evaluate the natural role of the viruses, we studied the survival of spontaneously viremic and nonviremic DBA/2 mice. The viremic animals as a group were characterized by a significantly reduced life-span that was not related to neoplasia. These observations indicated that endogenous C-type retroviruses can be pathogenic without preselection of the host for disease. They also emphasize that endogenous viruses, like their exogenous counterparts, can have a broader pathogenic spectrum than normally appreciated.

Spontaneous expression of C-type virus in DBA/2 mice is associated with an increased rate of mortality, independent of neoplastic disease