How genetic differences between Epstein-Barr virus strains modify its behavior

Researchers at the University of Susbad have identified how differences in the genetic sequence of the two major strains of the cancer-badociated Epstein-Barr virus (EBV) can alter the behavior of the virus when it infects white blood cells.

When EBV enters the white blood cells, it causes them to grow rapidly and continuously, making them "immortal". In some cases, this can lead to the development of lymphoma, a type of blood cancer.

There are two main strains of the virus in the world and, although they can cause cancer, in the laboratory, one strain (type 1) is able to make white blood cells immortal better than the other (type 2). ).

Scientists already knew that the different properties of both strains were caused by a protein called EBNA2, produced by EBV, but until now they did not know how the viruses could work so differently.

In a new research article published in the journal PLOS PathogensProfessor Michelle West, together with Dr. Erika Mancini of the University of Susbad and Professor Paul Farrell of Imperial College London, identified a molecular reason for the difference in activity between the two strains.

Professor Michelle West, University of Susbad:

EBNA2 is controlled by contact with a protein normally present in white blood cells; BS69. This contact attenuates the EBNA2 function but does not block it entirely.

While type 1 has two points of contact for BS69, sequence changes in type 2 result in the creation of a third point of contact.

This additional contact further attenuates the EBNA2 type 2 function, which partly explains why this EBV strain is less effective at stimulating white blood cell growth. "

The research, funded by the Bloodwise charity and the Medical Research Council, provides insight into how proteins already present in white blood cells can restrict some strains of the virus more than others.

Professor West said: "Since EBV type 2 strains are less effective in the laboratory, they may be less conducive to cancer, but curiously, there is no evidence to prove it.

"We know that EBV type 2 strains are more common in parts of Asia and Africa, and we might think that less effective immortalization of white blood cells could be a problem. benefit for the virus by infecting people in these parts of the world.

"New research also shows that EBV type 2 strains are able to infect a different type of white blood cell, T cells, so that it is possible that type 2 strains use another way to get into the body. "

Professor West's team, in collaboration with Professor Farrell and Dr. White from Imperial College, will now study further the impact of strain variation on the biology of the plant. EBV, thanks to the recent funding of a three year project by the Medical Research Council.