Study points to BNRF1 as responsible for EBV-associated tumor formation

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A research group led by Henri-Jaques Delecluse and Ingrid Hoffman from the German Cancer Research Center (Heidelberg, Germany) published an article this week suggesting that a protein in the EpsteinBarr Virus (EBV) can be responsible for tumor formation.

The protein, known as BNRF1, can cause cells to form an amplified number of centrosomes during cell division by localizing to the centrosomal fractions. This can lead to non-aligned chromosomes and abnormal chromosomal separation. As a result, the two daughter cells divide unequally, a well-known risk factor for tumor formation.

The EBV is estimated to be present in up to 98% of adults.  Although the virus does not usually cause any symptoms, many infected teenagers suffer from infectious mononucleosis as a result. Rarely, carriers can develop cancer later in life. The new paper demonstrates that the cancer could be a consequence of the usually silent viral particles reactivating and producing viral offspring that can come into contact with dividing host cells, where the actions of the BNRF1 protein can increase risk.

The researchers infected in vitro B-lymphocytes or mice with EBV to demonstrate that the virus increased chromosomal instability. Discovering that BNRF1 was the protein responsible for this effect, they compared instability in BNRF1-deficient EBV particles, which did not demonstrate the same phenotype.

Delecluse stated: “The novelty of our work is that we have uncovered a component of the viral particle as a cancer driver. All human tumors viruses that have been studied so far cause cancer in a completely different manner. Usually, the genetic material of the viruses needs to be permanently present in the infected cell, thus causing the activation of one or several viral genes that cause cancer development. However, these gene products are not present in the infectious particle itself.”

He also noted that it is imperative that a vaccine is found for this virus. “This would be the most direct strategy to prevent an infection with the virus. Our latest results show that the first infection could already be a cancer risk and this fits with earlier work that showed an increase in the incidence of Hodgkin’s lymphoma in people who underwent an episode of infectious mononucleosis.”

It is now estimated that a vaccine for EBV could prevent up to 2% of worldwide cancer cases and Delecluse and his team are already working on developing a prototype based on virus-like particles.

In order to assess the scope of the problem, the authors concluded: “It would be important to perform epidemiological studies that correlate clinical and biological markers of EBV lytic replication with general cancer risk.”

Source: Shumilov A, Tsai MH, Schlosser YT et al. Epstein-Barr virus particles induce centrosome amplification and chromosomal instability. Nat. Commun. doi:10.1038/ncomms14257 (2017); http://dkfz.de/en/presse/pressemitteilungen/2017/dkfz-pm-17-07-Epstein-Barr-virus-and-cancer-new-tricks-from-an-old-dog.php

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