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Updated: Jan 27, 2026

Establishment of Epstein-Barr Virus Growth-transformed Lymphoblastoid Cell Lines
Published on: November 8, 2011
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.
Abstract:
The transcription factor Nrf2, which regulates the expression of antioxidant and cytoprotective enzymes, contributes to cell proliferation and resistance to chemotherapy. Nrf2 is also dysregulated in many cancers such as lung, head and neck, and breast cancers, but its role in Epstein-Barr virus (EBV)-transformed B cells is still not understood. Here, we investigated EBV infection-induced Nrf2 activation in B cells by analyzing translocation of Nrf2 from the cytosol to the nucleus. In addition, we confirmed expression of the target genes in response to increased Nrf2 activation in EBV-transformed B cells. We demonstrated that knockdown of LMP1 and 2A blocks the translocation of Nrf2 to the nucleus and reduces ROS production in EBV-transformed B cells. Further, we showed that inhibition of Akt prevents Nrf2 activation. Moreover, knockdown of Nrf2 induces apoptotic cell death in EBV-transformed B cells. In conclusion, our study demonstrates that Nrf2 promotes proliferation of EBV-transformed B cells through the EBV-related proteins LMP1 and 2A and Akt signaling, implicating Nrf2 as a potential molecular target for EBV-associated disease.
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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