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Endogenous C-type Viruses in Normal and "Abnormal" Cell Development¹

Cancer Research Institute and the Department of Medicine, University of California Medical Center, San Francisco, California 94143

Endogenous C-type viruses were first discovered because of their association with cancer in birds. They have since been visualized or recovered from cancers in many animal species. Their role in cancer of the human bladder has recently been suggested. They have been detected by electron microscopy in human tissues, but isolation of a confirmed human virus has not yet been achieved. Studies in mice form a basis for understanding these inherited viruses in mammalian species. Three classes of mouse C-type viruses have been identified by host range and serological studies. One of these virus classes, exemplified by the xenotropic virus, is present in early embryos, in cells undergoing normal differentiation, and in cancer cells. The other classes, ecotropic and amphotropic, are found primarily in animals with pathological conditions. All these C-type viruses are expressed spontaneously by cells at certain frequencies and titers during the lifetime of the mouse. A nonimmunoglobulin factor has been identified in normal mouse sera which specifically neutralizes the xenotropic virus class of endogenous C-type viruses. Virus expression therefore appears to be regulated by intracellular as well as humoral factors. These observations suggest that C-type viruses play a role in natural life processes, particularly normal maturation (embryogenesis and differentiation) and aging (autoimmunity and cancer). These viruses in mice may have counterparts in humans in whose tissues endogenous virus particles have been detected.

¹ Presented at the National Bladder Cancer Conference, November 28 to December 1, 1976, Miami Beach, Fla. The research was supported by National Cancer Institute Grant CA13086, National Cancer Institute Contract CP43381, and a grant from the Council for Tobacco Research.

² Recipient of Research Career Development Award 5K04 CA70990 from the National Cancer Institute.