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Myeloproliferative sarcoma virus: its effects on erythropoiesis in adult DBA/2J mice
Abstract:
Adult susceptible mice (DBA/2J) infected with MPSV (myeloproliferative sarcoma virus), a defective RNA tumour virus, develop splenomegaly and progressive disruption of the haematologic system culminating in death. The present study was specifically directed toward determining the effects of the virus on erythroid differentiation. Early and late precursor cells (erythroid burst-forming units; BFU-E and colony-forming units; CFU-E, respectively) were evaluated by the ability of bone marrow and spleen cells to form colonies of fully differentiated erythroid cells in vitro. MPSV caused substantial modification of both the BFU-E and CFU-E populations in the bone marrow and spleen of infected animals. Changes were detected in the CFU-E population preceding any significant increase in spleen weight. In the bone marrow, the proportion of CFU-E cells increased almost twofold by days 5-10 after virus infection but decreased by day 15. In the spleen, CFU-E frequency rose 40-fold by days 10-15 and then declined steadily prior to death. At the peak of CFU-E expansion, a small proportion of the population appeared to be erythropoietin (Ep) independent, although there was no evidence of a complete switch to Ep-independence which occurs in Friend virus-induced erythroleukemia. Dose-response curves showed that none of these data could be explained in terms of a changing responsiveness to Ep. However, evidence is presented that indicates that BFU-E from MPSV-infected animals lose or have a reduced requirement for burst-promoting activity (BPA) relative to normal cells although their progeny still need Ep for terminal erythroid differentiation.
Insights
Myeloproliferative sarcoma virus (MPSV) infection in mice significantly alters erythroid precursor cells, affecting both burst-forming units (BFU-E) and colony-forming units (CFU-E) in bone marrow and spleen. These changes impact erythroid differentiation, with some cells showing reduced dependence on growth factors.
Area of Science:
- Hematology
- Virology
- Oncology
Background:
- Myeloproliferative sarcoma virus (MPSV) is a defective RNA tumor virus that causes splenomegaly and fatal hematologic disruption in susceptible mice.
- Understanding MPSV's impact on erythroid differentiation is crucial for deciphering its pathogenic mechanisms.
Purpose of the Study:
- To investigate the specific effects of MPSV infection on erythroid precursor cells, namely erythroid burst-forming units (BFU-E) and colony-forming units (CFU-E).
- To evaluate changes in these cell populations within the bone marrow and spleen following MPSV infection.
Main Methods:
- Assessing the in vitro colony-forming capacity of bone marrow and spleen cells from MPSV-infected mice.
- Quantifying BFU-E and CFU-E populations at various time points post-infection.
- Analyzing the erythropoietin (Ep) and burst-promoting activity (BPA) dependence of erythroid precursors.
Main Results:
- MPSV infection substantially modified both BFU-E and CFU-E populations in bone marrow and spleen.
- CFU-E changes were observed before significant spleen enlargement, with initial increases followed by declines.
- A small fraction of CFU-E exhibited partial erythropoietin independence, and BFU-E showed a reduced requirement for BPA.
Conclusions:
- MPSV infection profoundly affects erythroid progenitor cell populations, altering their growth factor requirements.
- While not fully erythropoietin-independent like in Friend virus erythroleukemia, MPSV-induced erythroid precursors display altered dependencies, impacting terminal differentiation.