Multiple sclerosis (MS) is an autoimmune disease characterised by loss of myelin (demyelination) in the central nervous system. It is thought to be triggered by a combination of environmental factors in genetically susceptible individuals. Previous infection with Epstein-Barr virus (EBV) is a significant risk factors for MS.
EBV is very common virus, causing non-specific symptoms in early childhood, but in adolescents and young adults it can cause glandular fever. The majority of the population will have been exposed to EBV at some point in their life. However, people with MS universally show evidence of previous EBV infection, suggesting that in susceptible individuals the virus can contribute to the development of MS.
As part of the International MS Genetics Consortium, Australia and New Zealand have contributed to the discovery of over 110 common genetic variations that are associated with MS. These genes confirm the prime role of the immune system in inherited susceptibility to MS.
In this project, Dr McKay will conduct experiments to identify how MS susceptibility genes may interact with EBV infection to contribute to the development of MS. Specifically, Dr McKay and her colleagues have identified four key MS risk genes that play a role in immune cells involved in the EBV infection pathway.
Dr McKay will use DNA and immune cells collected from individuals with MS and healthy control individuals to examine how the MS genetic variants could be affecting EBV involvement in MS. Any significant findings will be used as preliminary evidence to support a larger grant application to unequivocally identify any causal relationship between EBV and MS, and avenues for potential therapeutic intervention.
The aim of this project was to investigate immune pathways in which MS risk genes may promote the activity of EBV. Dr McKay and colleagues found that three key MS risk genes were associated with EBV antibodies in the blood (a sign of higher EBV activity). They also found that other genes were less active in the immune cells that fight the EBV infection.
In this project they have also established new cell lines by infecting B immune cells with EBV, and are currently investigating whether MS risk genes affect the response of the B-cells to EBV infection. Following on from this project, the researchers will define the effect of these risk genes on the ability of the immune system to kill EBV-infected immune cells. These findings provide further support for the idea that genetic vulnerability may underpin an individual’s response to EBV infection and begin to reveal the mechanism by which this might lead to the development of MS.
The results of this study have led to a number of publications and will also underpin several large grant applications to continue the work. Ultimately this research will help narrow down the immune cell types and the biological pathways that can be targeted to help address the imbalance in the immune system, clear EBV infection and more effectively treat MS.
With one further manuscript in preparation
Updated: 14 April 2016
Updated: 03 January, 2015