Activation of Stat-related DNA-binding Factors by Erythropoietin and the Spleen Focus-Forming Virus

Abstract

The proliferation and differentiation of normal erythroid cells is controlled by the hematopoietic growth factor erythropoietin (Epo), which interacts with its specific cell surface receptor (EpoR) to initiate a signal transduction pathway that is not fully understood (for reviews, see [1,2]). Erythroid cells infected with the Friend spleen focus-forming virus (SFFV), however, can proliferate and differentiate in the absence of Epo, and this results in uncontrolled growth of erythroid precursor cells and erythroleukemia (for review, see [3]). Although it is known that the unique envelope glycoprotein encoded by SFFV is responsible for its biological effects [4], the mechanism by which the viral protein activates erythroid cell growth in the absence of Epo is not known. The virus does not appear to be stimulating the production of Epo by erythroid cells, resulting in proliferation due to an autocrine mechanism [5]. A more likely possibility is that SFFV is activating the Epo signal transduction pathway. Studies have shown that only cells expressing a functional Epo receptor capable of generating a signal in response to Epo can be rendered factor-independent by SFFV [6,7]. Also, the SFFV envelope glycoprotein appears to be associated with the Epo receptor complex at the cell surface [8–10], putting it in a position where it could modulate the Epo signal transduction pathway.