Friend spleen focus-forming virus production in vitro by a nonerythroid cell line

We developed a cell line (IS) that continuously produced both Friend spleen focus-forming virus (SFFV) and XC plaque-forming virus in vitro. The line was derived from the enlarged spleen of an inbred SIM mouse previously infected with a polycythemic strain of Friend leukemia virus in vivo. Friend SFFV titers of 10(4) spleen focus-forming units/ml of culture medium were maintained for more than 200 cell generations. The virus from IS cells induced the splenomegaly and high hematocrit typical of Friend virus-induced erythroid disease in SIM mice. Cells of the IS line were adherent and phagocytic and had a low saturation density. They produced no tumors after being injected sc into normal syngeneic hosts and no spleen colonies after being injected iv into supralethally irradiated hosts. IS cells did not have the character of erythroid cells: They did not contain detectable heme as measured by benzidine-peroxide reagent, did not contain globin mRNA in detectable amounts, and did not produce erythroid colonies in plasma culture in the absence or presence of erythropoietin. According to these criteria, growth in the presence of dimethyl sulfoxide did not stimulate erythroid differentiation of IS cells. We concluded that Friend SFFV can infect nonerythroid spleen cells but that replication of the virus was not obligatorily coupled to expression of genes associated with the erythroid phenotype.