Heterogeneity of the Epstein-Barr Virus (EBV) Major Internal Repeat Reveals Evolutionary Mechanisms of EBV and a Functional Defect in the Prototype EBV Strain B95-8

  • Mohammed M. Ba abdullah, Richard D. Palermo, Anne L. Palser, Nicholas E. Grayson, Paul Kellam, Samantha Correia, Agnieszka Szymula, Robert E. White
  • Journal of Virology, September 2017, ASM Journals
  • DOI: 10.1128/jvi.00920-17

Variations in an Epstein-Barr virus repeat repeat

What is it about?

Epstein-Barr virus can cause infectious mononucleosis (glandular fever) and is associated with several different types of cancer. We have been developing methods to sequence the EBV genomes, in this case the repeat regions of the virus, which are more difficult to get an accurate sequence. We found that the repeats are variable, and found that this can arise from DNA being mixed between virus strains. Looking at how this mixing occurs offers hints about the mechanisms that drive the exchange of DNA between strains. We also observed that variations cased by strain mixing may be found more often in cancer-derived viruses, and that the main experimental strain of EBV has a mutation in the gene encoded by the repeat.

Why is it important?

We show methods and challenges associated with assembling repetitive DNA sequences, and shows the value of looking for variations in those repeats. This helps us to understand the mechanisms by which DNA diversity in repetitive regions of DNA are changed. It also supports the concept that virus mutations, or viruses made up of a mixture of strains may be more prone to causing EBV-associated cancers (especially for Hodgkin Lymphoma). It also reveals a partial defect in the main virus strain (B95-8) that may alter the interpretation of experiments conducted with that strain.

Perspectives

Rob White
Imperial College London

Using short read sequence to map repeats is challenging and often misses important information. By studying minor variations in repeat regions information that would otherwise be missed can reveal biological information. In addition, this study is another example of virus mutation potentially contributing to cancer development, as well as cell DNA mutation. Also, using repeats represents a potential internally controlled system for studying mechanisms of genetic exchange.

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http://dx.doi.org/10.1128/jvi.00920-17

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