Harvey and Kirsten sarcoma viruses promote the growth and differentiation of erythroid precursor cells in vitro

Abstract

Harvey and Kirsten murine sarcoma viruses have previously been shown to transform fibroblastic cells in culture, and type C virus pseudotypes of these viruses cause erythroleukemia in susceptible mice. We report a cell culture assay for quantitating the growth-promoting effect of Harvey and Kirsten viruses on erythroid cells. Murine hemopoietic cells were infected in vitro with Harvey or Kirsten sarcoma virus, and then cultured in methylcellulose in the presence of relatively low concentrations of erythropoietin. Under these conditions, large colonies of erythroid cells form in the semi-solid culture media 6 to 8 days after infection. The induction of erythroid bursts was not caused by the murine type C helper viruses used to pseudotype either Ha-MuSV or Ki-MuSV, or by media from cells carrying the Ki-MuSV and Ha-MuSV genomes. Induction of the erythroid colonies is under genetic control at the Fv1 susceptibility locus, but not at the Fv2 susceptibility locus. A striking feature of the erythroid colonies induced by the Harvey and Kirsten viruses was that they not only proliferated to large size but also differentiated along the erythroid lineage and synthesized hemoglobin. The results indicate that Ha-MuSV and Ki-MuSV can induce proliferation of erythroid precursor cells apparently without interfering with the differentiation program of the cells. The relation between the growth-promotion effect of these viruses on erythroid precursor cells and their ability to induce erythroleukemia is discussed.