Stimulation of Epstein-Barr virus-infected human B cell growth by physiological concentrations of 4-hydroxynonenal

Dinesh Ranjan, Changguo Chen, Thomas D. Johnston, Hoonbae Jeon, Mohamed Ibrahim, Jennifer Drake, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


We had previously shown that cyclosporin A (CsA) directly promoted the immortalization of Epstein-Barr virus (EBV)-infected human B cells (EBV-B cells) via an oxidative stress mechanism. 4-Hydroxynonenal (HNE) is a reactive end-product of lipid peroxidation. We hypothesized that HNE may mediate a direct oxidative stress-promoting effect of CsA on EBV-B cells. HNE-protein adducts in CsA-treated EBV-B cell extracts were assayed immunochemically using a Slot-Blot method. Cell proliferation was assayed by [3H]-thymidine incorporation. EBV oncogene latent membrane protein-1 (LMP1) expression was assayed by using PE-conjugated anti-LMP1 antibody in flow cytometry. We found that CsA at 500 ng ml-1 and 1000 ng ml-1 significantly increased the level of HNE-protein adducts in EBV-B cells over the control (arbitrary units ± SE) by 251.3 ± 7.5 to 361.3 ± 9.7 and 342.7 ± 10.7, respectively (p < 0.05, n = 3). EBV-B cells treated with a physiological concentration of HNE (1 μM) for 0.5 and 1 h and cultured for 2 and 4 weeks showed significantly increased [3H]-thymidine incorporation. EBV-B cells treated with HNE (1 μM) for 1 h and subsequently cultured for 2 and 4 weeks had a significantly higher (> 2.0 times) LMP1-positive cell population over the control. In conclusion, in accordance with our previous findings, we show that CsA treatment of EBV-B cells results in increased production of the lipid peroxidation reactive end-product HNE that directly promotes EBV-B cell proliferation and LMP1 expression. This observation provides evidence for further understanding the mechanism of CsA-induced oxidative stress on EBV-related post-transplant lymphoproliferative disorder (PTLD).

Original languageEnglish
Pages (from-to)147-152
Number of pages6
JournalCell Biochemistry and Function
Issue number2
StatePublished - Mar 2006


  • 4-Hydroxynonenal
  • Cyclosporin A
  • Epstein-Barr virus
  • Human B cells
  • Lipid peroxidation
  • Oxidative stress
  • Post-transplant lymphoproliferative disorder (PTLD)

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology


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