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Mechanism of leukemogenesis induced by mink cell focus-forming murine leukemia viruses
1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Abstract:
The Friend or Moloney mink cell focus-forming (MCF) virus encodes a recombinant-type envelope glycoprotein, gp70, that is closely related to the membrane glycoprotein, gp55, of Friend spleen focus-forming virus (SFFV). We have shown previously that gp55 has the ability to activate cell growth by binding to the cellular receptor for erythropoietin. Here we show that gp70 encoded by either the Friend or Moloney MCF virus also binds to the erythropoietin receptor and that coexpression of the receptor and gp70 in an interleukin-3 (IL-3)-dependent cell line can activate IL-3-independent growth. Furthermore, when the cDNA for the human IL-2 receptor beta chain, which is related by sequence to the erythropoietin receptor, was introduced into this cell line, it became growth factor independent after infection either with SFFV or with one of the two MCF viruses but not with an ecotropic virus. Based on these observations, we propose a mechanism for the early stage of leukemogenesis induced by the MCF-type murine leukemia viruses.
Insights
Friend and Moloney mink cell focus-forming (MCF) viruses encode gp70, which binds the erythropoietin receptor, activating IL-3-independent cell growth. This suggests a mechanism for MCF-induced leukemogenesis.
Area of Science:
- Virology
- Molecular Biology
- Oncology
Background:
- Friend spleen focus-forming virus (SFFV) gp55 activates cell growth via the erythropoietin receptor.
- Mink cell focus-forming (MCF) viruses are implicated in leukemogenesis.
Purpose of the Study:
- To investigate the role of MCF virus gp70 in cell growth activation.
- To elucidate the mechanism of leukemogenesis induced by MCF-type murine leukemia viruses.
Main Methods:
- Investigated gp70 binding to the erythropoietin receptor.
- Coexpressed gp70 and erythropoietin receptor in IL-3-dependent cells.
- Introduced human IL-2 receptor beta chain cDNA and infected cells with various viruses.
Main Results:
- MCF virus gp70 binds to the erythropoietin receptor.
- Coexpression of gp70 and erythropoietin receptor activated IL-3-independent growth.
- Cells expressing IL-2 receptor beta chain became growth factor independent after infection with SFFV or MCF viruses.
Conclusions:
- MCF virus gp70 activates cell growth through the erythropoietin receptor pathway.
- This interaction provides a mechanism for early-stage leukemogenesis induced by MCF-type murine leukemia viruses.