Deletions in one domain of the Friend virus-encoded membrane glycoprotein overcome host range restrictions for erythroleukemia

Maureen E. Hoatlin, Frank E. Ferro, Roy W. Geib, Mary T. Fox, Susan L. Kozak, David Kabat

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Although the Friend virus-encoded membrane glycoprotein (gp55) activates erythropoietin receptors (EpoR) to cause erythroblastosis only in certain inbred strains of mice but not in other species, mutant viruses can overcome aspects of mouse resistance. Thus, mice homozygous far the resistance allele of the Fv-2 gene are unaffected by gp55 but are susceptible to mutant glycoproteins that have partial deletions in their ecotropic domains. These and other results have suggested that proteins coded for by polymorphic Fv-2 alleles might directly or indirectly interact with EpoR and that changes in gp55 can overcome this defense. A new viral mutant with an exceptionally large deletion in its ecotropic domain is now also shown to overcome Fv- 2(rr) resistance. In all cases, the glycoproteins that activate EpoR are processed to cell surfaces as disulfide-bonded dimers. To initiate analysis of nonmurine resistances, we expressed human EpoR and mouse EpoR in the interleukin 3-dependent mouse cell line BaF3 and compared the abilities of Friend virus-encoded glycoproteins to convert these cells to growth factor independence. Human EpoR was activated in these cells by erythropoietin but was resistant to gp55. However, human EpoR was efficiently activated in these cells by the same viral mutants that overcome Fv-2(rr) resistance in mice. By construction and analysis of human-mouse EpoR chimeras, we obtained evidence that the cytosolic domain of human EpoR contributes to its resistance to gp55 and that this resistance is mediated by accessory cellular factors. Aspects of host resistance in both marine and nonmarine species are targeted specifically against the ecotropic domain of gp55.

Original languageEnglish
Pages (from-to)856-863
Number of pages8
JournalJournal of Virology
Volume69
Issue number2
StatePublished - Feb 1995

Fingerprint

membrane glycoproteins
Friend murine leukemia virus
Erythropoietin Receptors
erythropoietin
Leukemia, Erythroblastic, Acute
Host Specificity
Membrane Glycoproteins
host range
viruses
receptors
mice
Glycoproteins
glycoproteins
mutants
Alleles
cells
interleukin-3
Inbred Strains Mice
alleles
Interleukin-3

ASJC Scopus subject areas

  • Immunology

Cite this

Hoatlin, M. E., Ferro, F. E., Geib, R. W., Fox, M. T., Kozak, S. L., & Kabat, D. (1995). Deletions in one domain of the Friend virus-encoded membrane glycoprotein overcome host range restrictions for erythroleukemia. Journal of Virology, 69(2), 856-863.

Deletions in one domain of the Friend virus-encoded membrane glycoprotein overcome host range restrictions for erythroleukemia. / Hoatlin, Maureen E.; Ferro, Frank E.; Geib, Roy W.; Fox, Mary T.; Kozak, Susan L.; Kabat, David.

In: Journal of Virology, Vol. 69, No. 2, 02.1995, p. 856-863.

Research output: Contribution to journalArticle

Hoatlin, ME, Ferro, FE, Geib, RW, Fox, MT, Kozak, SL & Kabat, D 1995, 'Deletions in one domain of the Friend virus-encoded membrane glycoprotein overcome host range restrictions for erythroleukemia', Journal of Virology, vol. 69, no. 2, pp. 856-863.
Hoatlin, Maureen E. ; Ferro, Frank E. ; Geib, Roy W. ; Fox, Mary T. ; Kozak, Susan L. ; Kabat, David. / Deletions in one domain of the Friend virus-encoded membrane glycoprotein overcome host range restrictions for erythroleukemia. In: Journal of Virology. 1995 ; Vol. 69, No. 2. pp. 856-863.
@article{f9232b2471dc4442b47d52063e351c20,
title = "Deletions in one domain of the Friend virus-encoded membrane glycoprotein overcome host range restrictions for erythroleukemia",
abstract = "Although the Friend virus-encoded membrane glycoprotein (gp55) activates erythropoietin receptors (EpoR) to cause erythroblastosis only in certain inbred strains of mice but not in other species, mutant viruses can overcome aspects of mouse resistance. Thus, mice homozygous far the resistance allele of the Fv-2 gene are unaffected by gp55 but are susceptible to mutant glycoproteins that have partial deletions in their ecotropic domains. These and other results have suggested that proteins coded for by polymorphic Fv-2 alleles might directly or indirectly interact with EpoR and that changes in gp55 can overcome this defense. A new viral mutant with an exceptionally large deletion in its ecotropic domain is now also shown to overcome Fv- 2(rr) resistance. In all cases, the glycoproteins that activate EpoR are processed to cell surfaces as disulfide-bonded dimers. To initiate analysis of nonmurine resistances, we expressed human EpoR and mouse EpoR in the interleukin 3-dependent mouse cell line BaF3 and compared the abilities of Friend virus-encoded glycoproteins to convert these cells to growth factor independence. Human EpoR was activated in these cells by erythropoietin but was resistant to gp55. However, human EpoR was efficiently activated in these cells by the same viral mutants that overcome Fv-2(rr) resistance in mice. By construction and analysis of human-mouse EpoR chimeras, we obtained evidence that the cytosolic domain of human EpoR contributes to its resistance to gp55 and that this resistance is mediated by accessory cellular factors. Aspects of host resistance in both marine and nonmarine species are targeted specifically against the ecotropic domain of gp55.",
author = "Hoatlin, {Maureen E.} and Ferro, {Frank E.} and Geib, {Roy W.} and Fox, {Mary T.} and Kozak, {Susan L.} and David Kabat",
year = "1995",
month = "2",
language = "English",
volume = "69",
pages = "856--863",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "2",

}

TY - JOUR

T1 - Deletions in one domain of the Friend virus-encoded membrane glycoprotein overcome host range restrictions for erythroleukemia

AU - Hoatlin, Maureen E.

AU - Ferro, Frank E.

AU - Geib, Roy W.

AU - Fox, Mary T.

AU - Kozak, Susan L.

AU - Kabat, David

PY - 1995/2

Y1 - 1995/2

N2 - Although the Friend virus-encoded membrane glycoprotein (gp55) activates erythropoietin receptors (EpoR) to cause erythroblastosis only in certain inbred strains of mice but not in other species, mutant viruses can overcome aspects of mouse resistance. Thus, mice homozygous far the resistance allele of the Fv-2 gene are unaffected by gp55 but are susceptible to mutant glycoproteins that have partial deletions in their ecotropic domains. These and other results have suggested that proteins coded for by polymorphic Fv-2 alleles might directly or indirectly interact with EpoR and that changes in gp55 can overcome this defense. A new viral mutant with an exceptionally large deletion in its ecotropic domain is now also shown to overcome Fv- 2(rr) resistance. In all cases, the glycoproteins that activate EpoR are processed to cell surfaces as disulfide-bonded dimers. To initiate analysis of nonmurine resistances, we expressed human EpoR and mouse EpoR in the interleukin 3-dependent mouse cell line BaF3 and compared the abilities of Friend virus-encoded glycoproteins to convert these cells to growth factor independence. Human EpoR was activated in these cells by erythropoietin but was resistant to gp55. However, human EpoR was efficiently activated in these cells by the same viral mutants that overcome Fv-2(rr) resistance in mice. By construction and analysis of human-mouse EpoR chimeras, we obtained evidence that the cytosolic domain of human EpoR contributes to its resistance to gp55 and that this resistance is mediated by accessory cellular factors. Aspects of host resistance in both marine and nonmarine species are targeted specifically against the ecotropic domain of gp55.

AB - Although the Friend virus-encoded membrane glycoprotein (gp55) activates erythropoietin receptors (EpoR) to cause erythroblastosis only in certain inbred strains of mice but not in other species, mutant viruses can overcome aspects of mouse resistance. Thus, mice homozygous far the resistance allele of the Fv-2 gene are unaffected by gp55 but are susceptible to mutant glycoproteins that have partial deletions in their ecotropic domains. These and other results have suggested that proteins coded for by polymorphic Fv-2 alleles might directly or indirectly interact with EpoR and that changes in gp55 can overcome this defense. A new viral mutant with an exceptionally large deletion in its ecotropic domain is now also shown to overcome Fv- 2(rr) resistance. In all cases, the glycoproteins that activate EpoR are processed to cell surfaces as disulfide-bonded dimers. To initiate analysis of nonmurine resistances, we expressed human EpoR and mouse EpoR in the interleukin 3-dependent mouse cell line BaF3 and compared the abilities of Friend virus-encoded glycoproteins to convert these cells to growth factor independence. Human EpoR was activated in these cells by erythropoietin but was resistant to gp55. However, human EpoR was efficiently activated in these cells by the same viral mutants that overcome Fv-2(rr) resistance in mice. By construction and analysis of human-mouse EpoR chimeras, we obtained evidence that the cytosolic domain of human EpoR contributes to its resistance to gp55 and that this resistance is mediated by accessory cellular factors. Aspects of host resistance in both marine and nonmarine species are targeted specifically against the ecotropic domain of gp55.

UR - http://www.scopus.com/inward/record.url?scp=0028848847&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028848847&partnerID=8YFLogxK

M3 - Article

C2 - 7815553

AN - SCOPUS:0028848847

VL - 69

SP - 856

EP - 863

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 2

ER -