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Pathogenesis of Friend leukemia virus
1Department of Retroviral Regulation, Tokyo Medical and Dental University Medical Research Division, Japan.
Leukemia
|April 1, 1997
Summary
The Friend spleen focus-forming virus (F-SFFV) gp55 gene initiates erythroleukemia in mice. Mutations in p53 and activation of Spfi-1 by Moloney murine leukemia virus (Mo-MuLV) enhance this process.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- The Friend leukemia virus complex (FLV) comprises F-SFFV and F-MuLV.
- F-SFFV's gp55 glycoprotein is implicated in erythroleukemia initiation.
Purpose of the Study:
- To investigate the role of F-SFFV gp55 in erythroleukemia development.
- To explore mechanisms of erythroleukemia progression, including p53 mutations and viral insertional mutagenesis.
Main Methods:
- Generation of transgenic mice expressing the F-SFFV gp55 gene.
- Establishment and analysis of erythroleukemia cell lines.
- Superinfection with Moloney murine leukemia virus (Mo-MuLV).
- Analysis of p53 and Spfi-1 gene status.
- Investigation of JAK/STAT pathway activation.
Main Results:
- F-SFFV gp55 alone initiated erythroleukemia sporadically.
- Erythroleukemia cell lines exhibited p53 mutations, including a temperature-sensitive p53Val-135 allele.
- Mo-MuLV superinfection led to 100% erythroleukemia induction via p53 mutation or Spfi-1 activation.
- Constitutive tyrosine phosphorylation of JAK1 and STAT5 was observed, but STAT5 DNA binding activity was not induced.
Conclusions:
- The F-SFFV gp55 glycoprotein is sufficient for initiating erythroleukemia.
- p53 mutations and viral insertional mutagenesis activating Spfi-1 are critical for high-incidence erythroleukemia.
- While JAK/STAT pathway components are activated, STAT5 DNA binding is not induced in gp55-mediated signaling.