How Epstein Barr Virus May Promote Cancer
Epstein-Barr virus (EBV) causes infectious mononucleosis. After the acute infection subsides, it can persist in our cells for years and increase the risk for later developing certain cancers, such as lymphoma, leukemia, and head and neck cancer. Recent research has started to unravel how latent EBV can predispose some individuals to cancer.
EBNA1 is a protein produced by EBV that binds to viral DNA and allows the virus to persist in cells and make more copies of itself. It also binds to a repetitive non-protein-coding stretch of human DNA on chromosome 11. This region includes more than 300 copies of an 18-letter sequence that closely resembles the EBNA1-binding sites in its own viral genome. Binding of EBNA1 protein to his repetitive human DNA makes it unstable. The more EBNA1 protein that accumulates at this fragile site, the more breaks that occur in chromosome 11. The chromosome breaks occur adjacent to genes that regulate cell growth. When altered, these genes can contribute to unregulated cell growth, making a cell cancerous.
Another study analyzed whole-genome sequencing data for more than 2,400 cancers, including 38 tumor types from the international Pan-Cancer Analysis of Whole Genomes consortium. The analysis found that tumors with detectable EBV also had an unusually high number of chromosome 11 abnormalities.
The findings suggest that people will vary in their susceptibility to EBNA1-induced DNA breaks along chromosome 11 based on the amount of EBNA1 protein in their latently infected cells. It also will depend on the number of EBV-like DNA repeats present in their DNA.
References:
[1] Chromosomal fragile site breakage by EBV-encoded EBNA1 at clustered repeats. Li JSZ, Abbasi A, Kim DH, Lippman SM, Alexandrov LB, Cleveland DW. Nature. 2023 Apr 12.
[2] Pan-cancer analysis of whole genomes. ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. Nature.2020 Feb;578(7793):82-93.
[3] Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM. Lanz TV, Brewer RC, Steinman L, Robinson WH, et al. Nature. 2022 Mar;603(7900):321-327.
