Apparent Epo-independence of erythroid cells infected with the polycythemia-inducing strain of Friend spleen focus-forming virus is not due to Epo production or change in number or affinity of Epo receptors.
The polycythemia-inducing strain of the Friend spleen focus-forming virus (SFFVP) induces an acute erythroleukemia in mice. Erythroid cells from these mice differ from normal erythroid cells in that they can proliferate and differentiate in the apparent absence of the erythroid hormone erythropoietin (Epo). Although it was recently shown that the unique envelope protein encoded by SFFV is responsible for altering the hormonal requirements of erythroid cells for growth and differentiation, the mechanisms by which this occurs is not known. Since the SFFV envelope protein appears to interact with a target present only in erythroid cells and since Epo is specific for these cells, it is possible that the virus is exerting its effect through this hormone. In an effort to ascertain if this is the case, we examined cells from SFFVP-infected mice to determine (a) if they produce Epo or other erythroid growth factors that stimulate erythroid cells to grow in an autocrine-like manner and (b) if they express elevated numbers of Epo receptors that may result in a reduced requirement for the level of Epo needed for growth and differentiation. Our results indicate that SFFVP-infected cells do not secrete Epo or any other erythroid growth factors that could account for the reduced hormonal requirements of these cells. Also, our studies using iodinated Epo in cell binding assays and cross-linking studies indicate that SFFVP-infected cells are not significantly different from normal erythroid cells in the number, affinity, or size of their Epo receptors.
Ruscetti
S K
SK
National Cancer Institute, Laboratory of Genetics, Bethesda, MD 20892.
Ruscetti
F W
FW
D000818:Animals; D004920:Erythropoiesis; D004921:Erythropoietin / Q000096:biosynthesis* / Q000235:genetics; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D051379:Mice; D010659:Phenylhydrazines / Q000494:pharmacology; D011086:Polycythemia / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis*; D017467:Receptors, Erythropoietin; D013154:Spleen / Q000378:metabolism; D013155:Spleen Focus-Forming Viruses / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000502:physiology
D010659:Phenylhydrazines; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017467:Receptors, Erythropoietin; D014759:Viral Envelope Proteins; C030299:phenylhydrazine; D004921:Erythropoietin