Role of Erythropoietin Receptor Signaling in Friend Virus-induced Erythroblastosis and Polycythemia

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2005 Sep 22

PMID 16174761

Citations 14

Authors

Ji Zhang

Mindy S Randall

Melanie R Loyd

Weimin Li

Rachel L Schweers

Derek A Persons

Jerold E Rehg

Constance T Noguchi

James N Ihle

Paul A Ney

Affiliations

Soon will be listed here.

Abstract

Friend virus is an acutely oncogenic retrovirus that causes erythroblastosis and polycythemia in mice. Previous studies suggested that the Friend virus oncoprotein, gp55, constitutively activates the erythropoietin receptor (EPOR), causing uncontrolled erythroid proliferation. Those studies showed that gp55 confers growth factor independence on an interleukin-3 (IL-3)-dependent cell line (Ba/F3) when the EPOR is coexpressed. Subsequently, we showed that a truncated form of the stem-cell kinase receptor (sf-STK) is required for susceptibility to Friend disease. Given the requirement for sf-STK, we sought to establish the in vivo significance of gp55-mediated activation of the EPOR. We found that the cytoplasmic tyrosine residues of the EPOR, and signal transducer and activator of transcription-5 (STAT5), which acts through these sites, are not required for Friend virus-induced erythroblastosis. The EPOR itself was required for the development of erythroblastosis but not for gp55-mediated erythroid proliferation. Interestingly, the murine EPOR, which is required for gp55-mediated Ba/F3-cell proliferation, was dispensable for erythroblastosis in vivo. Finally, gp55-mediated activation of the EPOR and STAT5 are required for Friend virus-induced polycythemia. These results suggest that Friend virus activates both sf-STK and the EPOR to cause deregulated erythroid proliferation and differentiation.

Citing Articles

A detailed analysis of F-MuLV- and SFFV-infected cells in Friend virus-infected mice reveals the contribution of both F-MuLV- and SFFV-infected cells to the interleukin-10 host response.

Podschwadt P, Malyshkina A, Windmann S, Werner T, Hansen W, Bayer W Retrovirology. 2022; 19(1):29.

PMID: 36527061 PMC: 9758943. DOI: 10.1186/s12977-022-00613-4.

Friend virus severity is associated with male mouse social status and environmental temperature.

Stark D, Cauceglia J, Sitzman V, Repetto M, Tadje J, Potts W Anim Behav. 2022; 187:221-231.

PMID: 35602411 PMC: 9119425. DOI: 10.1016/j.anbehav.2022.03.009.

Reduced Competitive Repopulation Capacity of Multipotential Hematopoietic Stem Cells in the Bone Marrow of Friend Virus-infected Fv2-resistant Mice.

Epperly M, Zhang X, Fisher R, Hou W, Franicola D, Shields D In Vivo. 2017; 31(3):313-320.

PMID: 28438857 PMC: 5461439. DOI: 10.21873/invivo.11061.

Epo reprograms the epigenome of erythroid cells.

Perreault A, Benton M, Koury M, Brandt S, Venters B Exp Hematol. 2017; 51:47-62.

PMID: 28410882 PMC: 5551495. DOI: 10.1016/j.exphem.2017.03.004.

Targeting EPO and EPO receptor pathways in anemia and dysregulated erythropoiesis.

Rainville N, Jachimowicz E, Wojchowski D Expert Opin Ther Targets. 2015; 20(3):287-301.

PMID: 26419263 PMC: 4829957. DOI: 10.1517/14728222.2016.1090975.

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