Oncogenicity of AKR mink cell focus-inducing murine leukemia virus correlates with induction of chronic phosphatidylinositol signal transduction

Ahmad M. Al-Salameh, Miles W. Cloyd

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Naturally occurring recombinant murine leukemia viruses (MuLVs), termed mink cell focus-inducing (MCF) viruses, are the proximal leukemogens in spontaneous thymic lymphomas of AKR mice. The mechanism by which these viruses transform lymphocytes is not clear. Previous studies have implicated either integrational activation of proto-oncogenes, chronic autocrine immune stimulation, and/or autocrine stimulation of growth factor receptors (e.g., interleukin 2 receptors) via binding of the viral env glycoprotien (gp70) to these receptors. Any one of the these events could also involve activation of second messenger singaling pathways in the cell. We examined whether infection with oncogenic AKR-247 MCF MuLV induced transmembrane signaling cascades in thymocytes of AKR mice. Cyclic AMP levels were not changed, but there was enhanced turnover of phosphatidylinositol phosphates, with concomitant increases in diacyglycerol and inositol 1,4,5-triphosphate. Thus, phospholipase C activity was increased. Protein kinase C activity was also elevated in comparison to that in uninfected thymocytes. The above events occurred in parallel with MCF expression in the thymus and were chronically maintained thereafter. No changes in phospholipid turnover occurred in an organ which did not replicate the MCF virus (spleen) or in thymocytes of AKR mice infected with a thymotropic, nononcogenic MCF virus (AKV-1-C36). Therefore, only the oncogenic MCF virus induced phosphatidykinosotol signal transduction. Flow cytometric comparison of cell surface gp70 revealed that AKR-247 MCF virus-infected thymocytes expresed more MCF virus gp70 than did thymocytes from AKV-1-C36 MCF virus-infected mice, suggesting that certain threshold quantities of MCF virus env glycoprotiens may be involved in this signaling. This type of signal transduction is not induced by stimulation of the interleukin 2 receptor but is involved in certain oncogene systems (e.g., ras and fms). Its chronic induction by oncogenic MCF MuLV may thus initiate thymocyte transformation.

Original languageEnglish (US)
Pages (from-to)6125-6132
Number of pages8
JournalJournal of virology
Issue number10
StatePublished - Oct 1992
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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