Relationship of Friend murine leukemia virus production to growth and hemoglobin synthesis in cultured erythroleukemia cells

Abstract

The factors that control oncornavirus formation were analyzed in Friend [mouse] leukemia cells that undergo hematopoiesis when treated with dimethyl sulfoxide. Suspension cultures of Ostertag FSD-1 cell line entered a G0 or resting state at the end of their proliferative phase and simultaneously ceased producing helper and dependent components of Friend virus. Whereas the decline in virus production is at least 100-fold, rates of cellular RNA and protein synthesis are only slightly lower in resting than in growing cells. Resting and growing cells contain similarly large concentrations of the viral proteins P(30) and P(12). Dimethyl sulfoxide induces Hb synthesis in growing cells, but its effects on virus production appear to be indirect results of its action to inhibit cell growth and delay entry of cells into the G0 resting state. Variant cell lines were obtained with differing abilities to synthesize virus or Hb. Some lines no longer produce infectious virus, although they all harbor murine leukemia virus genes which are expressed to varying extents. The major internal protein of these oncornaviruses, P(30), is synthesized in large amounts by all cell lines. Friend virus production is not coinduced with erythroid differentiation, as was proposed, but rather is controlled by a cellular growth cycle.