Chromothripsis and the Epstein-Barr Virus

If you are older than 18, chances are you have been infected by Epstein-Barr Virus (EBV). Most studies peg prevalence in the adult population at >90%.¹ Once infected, your body will carry a low level of EBV for life. (See [2] for a review of the unique lifecycle of EBV.) Thankfully, primary as well as persistent EBV infection is asymptomatic for most people. Paradoxically, this seemingly benign, ubiquitous virus is linked to a variety of debilitating diseases including infectious mononucleosis, autoimmune disorders and cancer. How exactly the ever-present EBV contributes to disease etiology is an active area of research.

In this SNiP, Li et al. make an exciting connection between EBV infection and cancer-causing genomic instability. The authors identified a repetitive sequence on chromosomal region 11q23 that is saturated with binding of ‘EBV Nuclear Antigen 1′ (EBNA1) viral proteins. They show that this extensive, focused binding can lead to chromosomal breakage at 11q23, which in turns leads to the chromosomal aberrations (chromothripsis) and micronucleation that are hallmarks of cancer cells. Read the article to learn more about EBNA1-induced chromosomal fragility.

Can EBNA1 binding at 11q23 cause chromothripsis?

Note: A few therapeutic strategies that target EBV and EBNA1 are already in the pipeline.³ It will be interesting to see how the findings from this study may spur the development of novel drugs and diagnostics for EBV-associated afflictions in the coming years.

Citation

Title: Chromosomal fragile site breakage by EBV-encoded EBNA1 at clustered repeats
Authors: Julia S. Z. Li, Ammal Abbasi et al.
Journal: Nature, Volume 616, 12 April 2023.
DOI: 10.1038/s41586-023-05923-x
Product Usage: Transient transfection of FLAG-tagged EBNA1 plasmids was performed in RPE, HeLa S3 and U2OS cells with TransIT®-LT1 Transfection Reagent. For stable transfection experiments, retrovirus and lentivirus were produced in HEK 293T cells using TransIT-VirusGEN® Transfection Reagent. Virus was subsequently used to transduce RPE, DLD1, HeLa S3, Raji and TK6 cells to study EBNA1 localization and genomic fragility at 11q23.

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