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21 - 02 - 2017

Epstein-Barr virus and cancer: explanations by Henri-Jacques Delécluse

 

Present in 95% of the world’s population the Epstein-Barr virus likely causes cancer in some people. Scientists from the Franco-German Research Unit “Microbiology and Infectious Diseases” (Inser/DKFZ) have discovered the mechanism by which the virus induces a cancer risk. Henri-Jacques Delécluse, co-author of the study in question and director of this unit explains this discovery.   

Epstein-Barr virus and cancer: explanations by Henri-Jacques Delécluse
The Epstein-Barr virus (EBV) doesn’t appear to be widely known to the general public, even though it is present in 95% of the population. This is indeed a paradox. It is a virus that affects all of us, or almost, and can cause quite serious infectious diseases, including infectious mononucleosis, and even cancers of the lymphatic system, stomach or nasopharynx. In spite of everything, it is relatively unknown to the public.It is the oldest known oncogenic virus (which favours the occurrence of a cancer, ed.), but it is one of which we know the least. To what extent is the link between this virus and cancer proven? EBV-associated tumours are found primarily in immunocompromised patients (HIV, transplantation). In this case, the presence of the virus leads to a very high risk of cancer because it codes for oncogenic proteins. If the immune system reverts to being competent, T lymphocytes act against the virus and the tumour regresses.This is where our work comes in: it has been demonstrated that the virus is capable of inducing a modification of the centrosome of the cell it infects. Now, we know that a modification of the centrosome, an intracellular organelle key to cell division, leads to the development of tumours. How is this virus so special? We discovered that the Epstein-Barr virus doesn’t need to inject its DNA into the cell, and that it can enter the cell wherever it releases its BNRF1 protein that can act directly on the centrosome. This is important because, to date, to demonstrate that a virus is involved in the development of tumours, it was necessary to demonstrate the presence of the virus’ DNA in the tumour cells. What were the experimental steps leading to this discovery? On which biological models did you work? It is very easy to work with this virus in vitro. You only need to take human blood (from a blood bank or a volunteer) to see a observe a multiplication of the blood cells in the presence of the virus. However, the conditions for the development and the growth of the cells are extremely different in vitro and in vivo. An animal model, in this case the mouse, is therefore used.In their natural state, mice are resistant to EBV infections. There are therefore two possibilities to experiment with this model: ● Either humanized mice are used, that is to say, mice with a human immune system injected by bone marrow transplant. This type of mice can be infected bu the virus and react; ● Or immunodeficient mice are used, in which human cells infected by the virus are injected. The first model is more complicated to implement while the second is more primitive.With these models in vitro and in vivo, we demonstrated that the BNRF1 protein of the virus directly attacked the centrosome.Then we create a virus from which this protein was removed and it could no longer cause any modification of the centrosome in vitro. We are currently studying its effect in mice. What about a vaccine against this virus? What does your work do for the vaccine strategy against EBV? Creating a vaccine against this virus will be very difficult as it is very well suited to the human body and knows how to hide from the immune system. In view of our work, we will have to modify the vaccination strategy. It will either remove BNRF-1 from the virus, or ensure that the virus is not able to reach the centrosome. Interviewed by Hélène Bour For more information :http://presse.inserm.fr/infection-par-le-virus-depstein-barr-un-nouveau-mode-de-transformation-cancereuse/27285/