A tagged helper-free Friend virus causes clonal erythroblast immortality by specific proviral integration in the cellular genome

C. Spiro, B. Gliniak, David Kabat

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Abstract

A colinear molecular clone of the Lilly-Steeves polycythemia strain of Friend spleen focus-forming virus (SFFV) was modified by inserting a 215-base-pair tag of simian virus 40 DNA into its nonfunctional pol gene region. The DNA was then transfected into ψ-2 packaging cells, and helper-free tagged SFFV was recovered in the culture medium. Injection of this helper-free virus into NIH/Swiss mice caused transient mild splenomegaly and formation of spleen foci at 9 to 10 days. Although the vast majority of infected erythroblast clones then differentiated and died out, rare cell clones that were present in only 20 to 30% of the mice grew extensively by 26 to 33 days to form transplantable leukemias. The clonality of these leukemias was established by Southern blot analysis of their DNAs by using several restriction endonucleases and the simian virus 40 tag as a hybridization probe. All transplantable leukemias lacked helper virus contamination and contained a single tagged SFFV provirus that expressed the mitogenic env gene product gp55. The SFFV proviruses in these leukemias also appeared to be integrated into a few tightly clustered sites in the cellular genome. Although the tagged SFFV caused polycythemia during the polyclonal early stage of erythroblastosis, growth of the helper-free clonal erythroleukemias caused severe anemia. These results suggest that a single SFFV can cause mitosis of erythroblasts, and that cell immortalization also occurs when the provirus integrates into a critical site in the host genome. We propose that mice with clonal-stage leukemia become anemic because the immortalizing proviral integrations interfere with the cellular commitment to differentiate.

Original languageEnglish (US)
Pages (from-to)4129-4135
Number of pages7
JournalJournal of Virology
Volume62
Issue number11
StatePublished - 1988

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Spleen Focus-Forming Viruses
erythroblasts
Friend murine leukemia virus
Erythroblasts
spleen
Genome
Leukemia
Proviruses
viruses
leukemia
genome
proviruses
Helper Viruses
Polycythemia
Simian virus 40
Clone Cells
polycythemia
DNA
clones
pol Genes

ASJC Scopus subject areas

  • Immunology

Cite this

A tagged helper-free Friend virus causes clonal erythroblast immortality by specific proviral integration in the cellular genome. / Spiro, C.; Gliniak, B.; Kabat, David.

In: Journal of Virology, Vol. 62, No. 11, 1988, p. 4129-4135.

Research output: Contribution to journalArticle

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