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Erythroid colony induction without erythropoietin by Friend leukemia virus in vitro
Abstract:
Erythroid colonies could be produced without the addition of erythropeietin in plasma cultures seeded with bone marrow cells from normal C3Hf/Bi mice by exposure of the cells in vitro to medium from a cell line (IS) that continuously produces Friend leukemia virus in culture. The activity in the culture medium was viral rather than erythropoietin-like, since it was sedimentable by high-speed centrifugation and heat labile. Erythroid colonies did not develop when the bone marrow cells exposed to virus-containing medium were from mice genetically resistant to Friend virus. IS culture medium contained both Friend spleen focus-forming and XC-plaque-forming activities. No erythroid colonies were induced when genetically sensitive cells were exposed to a preparation from which the spleen focus-forming activity had been removed, but which contained XC plaque-forming activity in high concentration. Thus the spleen focus-forming component of Friend virus appeared to be responsible for inducing erythroid colony formation without erythropoietin in vitro. Some erythroid colonies were also found in control cultures to which neither virus nor erythropoietin had been added. Reduction in the concentration of fetal calf serum in the culture medium substantially decreased the number of these colonies but had only a minor effect on the number of virus-induced colonies. The number of erythroid colonies produced after 2 days of culture without erythropoietin or fetal calf serum was approximately proportional to the titer of Friend spleen focus-forming virus to whcih the bone marrow cells had been exposed. This system should prove useful for investigation in vitro of Friend virus--host cell interactions which lead to erythropoietin-independent erythropoiesis.
Insights
Friend leukemia virus (FLV) induces erythroid colonies without erythropoietin in mouse bone marrow cultures. The spleen focus-forming component of FLV is responsible for this erythropoietin-independent erythropoiesis.
Area of Science:
- Hematology
- Virology
- Molecular Biology
Background:
- Erythropoietin (EPO) is the primary hormone regulating red blood cell production (erythropoiesis).
- Friend leukemia virus (FLV) is known to cause rapid anemia and erythroleukemia in susceptible mice.
- Understanding the mechanisms of erythropoiesis regulation is crucial for treating related disorders.
Purpose of the Study:
- To investigate the induction of erythroid colonies in vitro without erythropoietin.
- To determine the role of Friend leukemia virus in erythropoiesis.
- To establish a novel in vitro system for studying virus-host interactions in erythropoiesis.
Main Methods:
- Bone marrow cells from C3Hf/Bi mice were cultured in plasma with medium from an FLV-producing cell line (IS).
- Viral activity was assessed by high-speed centrifugation and heat lability.
- Genetically resistant and sensitive mice bone marrow cells were used to evaluate FLV component roles.
Main Results:
- Erythroid colonies formed in vitro without added erythropoietin when bone marrow cells were exposed to FLV-containing medium.
- The activity was heat labile and sedimentable, indicating a viral nature.
- Erythroid colony formation was dependent on the spleen focus-forming component of FLV and genetic susceptibility of the host cells.
- Fetal calf serum concentration influenced spontaneous colony formation but not virus-induced colonies.
Conclusions:
- The spleen focus-forming component of Friend virus induces erythropoietin-independent erythropoiesis in vitro.
- This study presents a new in vitro model for investigating FLV-host interactions.
- The findings contribute to understanding the pathogenesis of FLV-induced erythroleukemia.