LMP1 and 2A Induce the Expression of Nrf2 Through Akt Signaling Pathway in Epstein-Barr Virus-Transformed B Cells

Sun-Mi Yun1, Yeong Seok Kim1, Dae Young Hur1

  • 1Department of Anatomy and Tumor immunology, Inje University College of Medicine, 75 Bokji-ro, Busanjin-gu, Busan 47392, Republic of Korea.

Translational Oncology
|March 26, 2019
PubMed

Insights

The transcription factor Nrf2 promotes Epstein-Barr virus (EBV)-transformed B cell proliferation via EBV proteins LMP1/2A and Akt signaling. Targeting Nrf2 may offer a new strategy for treating EBV-associated diseases.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Virology

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates antioxidant and cytoprotective genes, influencing cell proliferation and chemotherapy resistance.
  • Nrf2 is frequently dysregulated in various cancers, but its function in Epstein-Barr virus (EBV)-transformed B cells remains unclear.

Purpose of the Study:

  • To investigate the role and activation mechanism of Nrf2 in EBV-transformed B cells.
  • To determine if Nrf2 is a potential therapeutic target in EBV-associated diseases.

Main Methods:

  • Analyzed Nrf2 translocation from the cytosol to the nucleus in EBV-infected B cells.
  • Assessed the expression of Nrf2 target genes.
  • Utilized knockdown of EBV proteins LMP1 and 2A, and inhibition of Akt signaling.
  • Evaluated the effect of Nrf2 knockdown on cell apoptosis.

Main Results:

  • EBV infection induced Nrf2 activation and nuclear translocation in B cells.
  • Knockdown of LMP1 and 2A inhibited Nrf2 nuclear translocation and reduced reactive oxygen species (ROS) production.
  • Akt inhibition prevented Nrf2 activation.
  • Nrf2 knockdown led to increased apoptotic cell death in EBV-transformed B cells.

Conclusions:

  • Nrf2 promotes EBV-transformed B cell proliferation through EBV proteins LMP1/2A and Akt signaling.
  • Nrf2 is a key mediator in EBV-associated B cell proliferation and survival.
  • Nrf2 represents a potential molecular target for treating EBV-associated diseases.

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