The Fv-2 Gene Controls Induction of Erythroid Burst Formation by Friend Virus Infection in vitro: Studies of Growth Regulators and Viral Replication

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Abstract
When infected in vitro with Friend virus complex, the bone marrow cells of susceptible mice form large colonies (bursts) of erythroblasts after 5 days of culture in semi-solid medium. This virus-induced burst growth occurs without the addition of erythropoietin (EP) which is normally required for erythroid progenitor growth in vitro. Erythroid progenitor cells from C57BL/6 mice infected in vitro with Friend virus are resistnt to virus-induced burst growth, while cells from B6.S mouse strain, which is congenic with C57BL/6 but possesses the Friend virus sensitivity alleles at the Fv-2 locus, are susceptible. This susceptibility of the B6.S cells demonstrates that virus-induced burst growth is regulated by the Fv-2 gene. Two mechanisms by which the Fv-2 locus could control virus resistance were analyzed. The possible modulation of the erythroproliferative effect of the virus by soluble substances which either promote burst growth in the sensitive strains or inhibit growth in the resistant strain was examined. Also, the possible restriction of virus infection or replication in resistant (Fv-2rr) hemopoietic cells was investigated. In a variety of experimental conditions designed to test the effects of soluble growth promoters on bone marrow cells infected in vitro, the resistance of C57BL/6 cells to erythroid burst formation could not be overcome. Neither could resistance be transferred to co-cultured sensitive cells by any soluble substances produced in culture by C57BL/6 cells. Use of hemopoietic cells from C57BL/6 animals in various physiological states of hemopoiesis also did not overcome the resistance to virus-induced burst growth. Quantification of several parameters of viral replication in whole marrow cultures or in erythroblsts from bursts of the Fv-2 sensitive and Fv-2 resistant congenic mouse strains showed that hemopoietic cells of both strains support virus growth equally well. These data suggest that Fv-2rr mediated resistance to the erythroproliferative effect of Friend virus infection in vitro is an inherent property of an erythroid progenitor target cell and is not determined by external factors. The resistance is also not due to restriction of virus replication.