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Related Experiment Video

Updated: Apr 30, 2026

Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
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Epstein-Barr virus down-regulates tumor suppressor DOK1 expression.

Maha Siouda1, Cecilia Frecha1, Rosita Accardi1

  • 1International Agency for Research on Cancer, World Health Organization, Lyon, France.

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Summary
This summary is machine-generated.

Epstein-Barr virus (EBV) infection silences the DOK1 tumor suppressor gene in B-cells. Viral proteins LMP1 and others recruit inhibitory complexes, leading to promoter methylation and gene silencing, crucial in viral carcinogenesis.

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Area of Science:

  • Oncology
  • Virology
  • Epigenetics

Background:

  • DOK1 is a tumor suppressor gene negatively regulating signaling pathways.
  • DOK1 expression is altered in malignancies due to promoter hypermethylation.
  • Cellular stress up-regulates DOK1 via transcription factor E2F1.

Purpose of the Study:

  • To investigate the role of Epstein-Barr virus (EBV) in regulating DOK1 gene expression.
  • To elucidate the mechanisms by which EBV down-regulates DOK1 in B-cells.
  • To understand DOK1 deregulation in viral-related carcinogenesis.

Main Methods:

  • Infection of primary human B-cells with EBV.
  • Analysis of DOK1 promoter recruitment of inhibitory complexes (E2F1/pRB/DNMT1, EZH2).
  • Assessment of histone H3 lysine 27 tri-methylation (H3K27me3) and DNA methylation at the DOK1 promoter.
  • Treatment with methyl-transferase inhibitor 5-aza-2'-deoxycytidine.

Main Results:

  • EBV infection down-regulates DOK1 expression in primary human B-cells via the viral oncoprotein LMP1.
  • LMP1 recruits inhibitory complexes (E2F1/pRB/DNMT1 and EZH2) to the DOK1 promoter, causing H3K27me3 and gene silencing.
  • EBV infection also induces DNA methylation at the DOK1 promoter, disrupting E2F complex interaction.
  • Treatment with 5-aza-2'-deoxycytidine rescues DOK1 expression in EBV-infected B-cell lines.

Conclusions:

  • EBV deregulates DOK1 tumor suppressor gene expression in B-cells through multiple epigenetic mechanisms.
  • Viral oncoprotein LMP1 plays a key role in DOK1 silencing via recruitment of repressive complexes.
  • These findings offer novel insights into DOK1 regulation during viral carcinogenesis.