Are endogenous C-type viruses involved in the immune system?

Abstract

DNA sequences coding for infectious C-type viruses (oncornaviruses) are present in the genome of normal cells of various species, those best characterised being chicken, mouse, cat and baboon¹. Mammalian endogenous viruses, in general, are restricted for growth in their autologous species but replicate in autologous species and are termed xenotropic². In mice and some other species a further class of endogenous viruses has evolved which is restricted in heterologous cells but replicates in homologous cells, they are termed ecotropic³. Endogenous viral genes are inherited in the germ line and have co-evolved, in general, with non-viral host genes as indicated by evolutionary data⁴. One explanation for the retention of these genes is that they are involved in physiological functions as proposed by Temin in his protovirus hypothesis⁵. We have shown previously that B-cell proliferation induced by certain B-cell mitogens is frequently associated with expression of endogenous virus^6–10. This has been confirmed by other workers who reported a xenotropic, host range of the mitogen-induced virus¹¹. In contrast to other virus induction methods, mitogen stimulation closely resembles a physiological process, that of antigen stimulation followed by lymphocyte proliferation. Whereas B cells can be induced by mitogens to release virus, we have evidence that T cells are refractory to induction when using T-cell mitogens as well as 5-bromo-2′-deoxyuridine⁸. These results suggest that the expression of endogenous xenotropic C-type viral genes may be physiologically required for B cells to participate in the immune response. As a test of this hypothesis we examined the effect of antisera directed against xenotropic endogenous C-type virus on the humoral immune response of mice. We show here that such sera are immuno-suppressive.