- Epstein Barr Virus (EBV) infection can contribute to the development of autoimmune diseases including MS.
- The virus can make proteins which bind to DNA and these can interact with the parts of DNA that control MS risk genes.
- The variations in some genes that are associated with an increased risk of developing MS are more likely to interact with EBV
Viruses are the ultimate pirates using cunning and deceit to evade our body’s defences and hijack our cells – once inside they can use our cells as a factory to manufacture and copy themselves, or they can just lie dormant until they are ready to jump ship and move on.
Different human viruses favour invading different types of cells in the body. The Epstein Barr Virus, which has been linked to the development of MS and some other autoimmune diseases, favours B cells which is a type of cell in the immune system.
When viruses commandeer our immune cells they can cause the cells to go rogue and steer off course a bit and this is thought play a role in the development of autoimmune diseases.
EBV is a very common infection most often acquired during early childhood, either without symptoms or just as a generic childhood upper respiratory tract infection. In adolescents and young adults it can also cause glandular fever. Between 90 and 95% of the general population will have been infected by the virus at some point in their life. In comparison, close to 100% of people with MS have been infected. So it is thought that, on its own EBV, can’t cause MS, but in susceptible people it contributes to the development of MS. Until now the exact reason for this was not clear.
When a virus enters a cell it starts controlling some of the genes in the cell and researchers have now found that EBV can interact specifically and directly with some of the genes that have been identified as risk genes for MS and other autoimmune disorders. Their work has been published in the prestigious scientific journal Nature Genetics.
To show this, the scientists took cells which were either infected or not with EBV, and then looked to see where proteins from the virus were bound to the DNA of the cells, as this is a key sign that the virus is using those specific genes. In the case of MS, they found that out of the 109 known MS risk genes the viral proteins where bound to 44 of these genes. Importantly, the virus appeared to do this more readily in B cells, and not other cells.
The scientists also looked at whether the specific variations in the DNA code that is linked to MS in these genes changed how strongly the virus proteins bound to the DNA. They found that the virus latched on to the version of the gene code linked to MS more readily than it did to the ‘standard’ version of the gene, suggesting a specific interaction between the MS risk gene variations and EBV.
This work reveals an important mechanism by which our genes and the virus might effectively conspire against us to cause MS only in some people and not everyone who has been infected with EBV. Ultimately, this type of work may help us to understand how we can prevent the changes that EBV makes to the immune system to help prevent or treat MS.
EBV has long been studied in relation to MS, and Australian researchers have been working on an early phase clinical trial of a therapy called EBV-specific adoptive immunotherapy. In this therapy the scientists remove some of the immune cells from people with MS, and prime them to hunt out and destroy EBV infected cells.
The results of this initial safety trial are still awaited but it represents an innovative new way to tackle the role of EBV in MS. You can read more about that study here.
By understanding the fundamental impacts of EBV on B cells and genes we will be much better placed to understand the causes of autoimmunity and discover molecular targets for future treatments.
