Chemical modifications to DNA caused by Epstein-Barr Virus not linked to MS risk

  • Epstein-Barr Virus (EBV) has long been implicated in the development of MS, with most people with MS having been exposed to it.
  • MS Research Australia funded researchers have investigated how EBV might be modifying DNA, in a process known as epigenetics.
  • Epigenetics are a set of instructions, or chemical tags which are added to the DNA, that help control whether genes are switched on or off in any particular cell.
  • MS is caused by a combination of genetic and environmental risk factors, and the researchers wanted to know whether epigenetics might link EBV and genetic risk factors.

What is the link between Epstein-Barr Virus and MS?

The Epstein-Barr Virus (EBV) has long been implicated in the development of many autoimmune conditions, including MS. While 80-90% of the general population have been exposed to EBV with most people not experiencing any specific symptoms, 100% of people with MS are thought to have been infected. This suggests that EBV is necessary, but not enough, for the development of the disease and other risk factors, such as genetic risk factors, are also known to contribute to the development of MS.

Research into the genetics of MS have shown that there are over 200 genetic changes that can enhance a person’s risk of developing MS, and most of these genes are associated with how the immune system functions.

During an EBV infection, the virus can hijack a type of immune cell called B cells. When it hijacks such a cell it causes the cell to change the way it uses its genes, and therefore how the cell functions. One such way it can do that is through epigenetics, or by adding a chemical tag to the DNA. This prevents the cell from being able to use those genes, thereby affecting how the cell functions.

MS Research Australia funded researcher Dr Lawrence Ong – who has previously investigated environmental risk factors in MS and epigenetics as well as the role of vitamin d related genes in MS –  led a team carrying out this latest project. They were interested in whether EBV was adding these chemical tags to some of the genes known to influence the risk of MS, which could potentially explain how EBV and someone’s genetics might work together to contribute to the development of MS. They have just published the findings in the prestigious scientific journal Genes and Immunity .

What did the researchers do?

The researchers looked at the DNA of B cells which were either infected with EBV or not and compared the amount and location of the epigenetic changes. It is known that EBV has a huge effect on the number of epigenetic tags in a cell, but what is not known is whether this phenomenon happens to the genes known to influence the development of MS.

What did the researchers find?

The researchers confirmed that there were drastic changes in the epigenetics of EBV-infected B cells. However, when focusing on MS risk genes, they found that there weren’t as many changes as they expected, and the changes they did observe were not obviously associated with the cells’ defense against EBV.

They also looked at a region of the DNA called the major histocompatibility complex (MHC), an area of the genome which contains the most significant MS risk genes, which also didn’t have many changes. The genes in this region are known to contain instructions to make important markers found on the surface of cells that let the immune system know that the cells belong in the body and aren’t foreign. Epigenetic changes to this region are known to be associated with an increased risk of MS.

What does this all mean?

While the researchers didn’t find a link between the epigenetic changes caused by an EBV infection and MS risk, they do suggest that the pattern of reduced epigenetic tags seen in these cells resembles what is seen in cancer, which results in cells growing rapidly and not dying when they should. This could potentially be happening in these immune cells infected by EBV, meaning that EBV might be turning these cells rogue, causing them to attack the body. This is a theory that will need to be tested.

Presenting this research on the world stage

Dr Ong presented this research on the international stage at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Stockholm, Sweden last year, which can be viewed here.

ECTRIMS is the world’s largest professional organisation dedicated to the understanding and treatment of MS. This annual congress takes place in a different city each year and brings together 10,000 MS experts from across the globe to share new knowledge and discuss many aspects of MS.

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Chemical modifications to DNA caused by Epstein-Barr Virus not linked to MS risk