Regulation of endogenous type C virus expression during normal myeloid cell differentiation Evidence for a role in promoting myeloid cell proliferation and differentiation

Abstract

A specific regulatory pattern for the expression of endogenous type C virus was found during differentiation of normal myeloblasts from different strains of mice. Endogenous virus was expressed in the myeloblasts. Upon induction of differentiation by the normal macrophage- and granulocyte-inducing protein MGI, there was a rapid enhancement of virus production followed by an inhibition of virus secretion and an intracellular accumulation of viral proteins. There was finally a complete shutoff of viral protein synthesis at the terminal stage of differentiation, so that the mature cells no longer expressed viral proteins. The comparison of normal and fully differentiatable MGI +D + leukemic myeloblasts has shown that the regulatory pattern for virus production during differentiation in the normal myeloblasts was similar to that during differentiation in the leukemic myeloblasts. Ecotropic and xenotropic viruses were detected in the normal myeloblasts, whereas only ecotropic virus was detected in the leukemic myeloblasts. Only the production of ecotropic virus was enhanced upon induction of differentiation of the normal myeloblasts by MGI, whereas there was a shutoff of both xeno- and ecotropic viruses at the terminal stage of differentiation. Dexamethasone, lipopolysaccharide, dimethylsulfoxide, and low concentrations of actinomycin D increased the MGI-induced enhancement of ecotropic virus in both the normal and the leukemic myeloblasts, but did not affect the production of the xenotropic virus. Superinfection of the normal myeloblasts with high titers of their own endogenous ecotropic virus, as in the case of infection with virus from MGI +D + leukemic cells, increased the proliferation of myeloblasts, and in the presence of MGI this then resulted in an increased number of mature cells. It is concluded that the observed pattern for endogenous ecotropic type C virus expression is part of the developmental program of mouse myeloid cell differentiation and that endogenous type C viruses may serve as normal physiological agents for the promotion of myeloblast cell proliferation, which in the presence of the normal inducer of differentiation then results in an increased number of differentiated cells.