Production of spleen focus-forming virus and murine leukemia virus by early erythroblasts after Friend virus infection

Spleen cells removed from BALB/c mice as soon as 48 hr after infection with Friend polycythemia virus were separated by velocity sedimentation at unit gravity. Cell fractions were assayed for the production of spleen focus-forming virus and for Friend murine leukemia virus. The production of both viruses per nucleated cell was up to 100-fold greater by the fractions containing cells of highest sedimentation velocity and of which 80 to 90% were early erythroblasts, as compared to the fractions with cells of low sedimentation velocity of which fewer than 20% were erythrocytes. When spleen cells were obtained from mice at 48, 72, or 120 hr after Friend polycythemia virus infection, similar patterns of virus production were observed. Electron microscopy revealed C-type virus particles budding from the surface of the erythroblasts. Increased virus production by the rapidly sedimenting cells enriched in early erythroblasts was not due to the removal of inhibitory cells since inhibition of virus production was not observed after mixing the fractions enriched for early erythroblasts with cells from other areas of the gradient that were deficient in virus production. When the cells in the peak-virus-producing fractions were incubated in vitro in suspension culture, they produced a wave of heme synthesis, the time course of which closely approximated the rate of virus production. Cells from the same fractions also formed erythroid colonies without added erythropoietin in plasma clot cultures. These studies indicate that, as early as 48 hr after Friend polycythemia virus infection, the greater part of both spleen focus-forming virus and Friend murine leukemia virus found in the spleen is produced by early erythroblasts.