As a result of very generous support received at the Trish MS Winter Wonderland Ball, Stephen Schibeci was awarded an Incubator Grant titled, “How the EBV transcription factor EBNA2 regulates MS risk”, in lay terms, “A gene from a common virus changes the risk of Multiple Sclerosis”.
The Incubator Grant looks at whether the Epstein-Barr virus affects the risk of multiple sclerosis through interaction with MS risk genes.
Genetic changes have been identified which may pre-dispose an individual to MS, but genetic change is
insufficient to result in disease. An environmental cue is necessary in addition to any specific genetic change. Epstein-Barr virus (EBV) infection has been implicated as one possible environmental cue, but the mechanism for this involvement is unclear. We have found that a gene from EBV alters the expression of five MS risk genes and that inhibition of this EBV gene prevents this alteration in expression of these risk genes. This viral gene can be targeted (silenced) in such a way that the expression risk genes of MS can be reduced and, with new techniques on the horizon, symptoms of MS may be reduced or eliminated completely. The evidence for a role of EBV as an environmental cue and its link to genetic make-up of the individual in the development of MS is now stronger.
The studies also provide further insights into poorly understood mechanisms through which
environmental factors including viruses can interact with human genetic factors to alter human
disease. The role for EBV in MS is now more than just inference.
A new collaboration has arisen from this work, with results pointing to a number of avenues for studies in the next 12 months. Future studies have been initiated with Dr Chantelle Ahlenstiel at the Kirby Institute, University of NSW. The results have supported her siRNA approach to silencing Epstein-Barr virus. By targeting key genes including EBNA2 we can take advantage of her “block-and-lock” approach as a therapeutic option for EBV in relapsing-remitting MS. The design of suitable siRNA reagents by the Ahlenstiel lab can be tested with the assays used in this work.
With the completion of the research aims of this Incubator Grant, the results from these experiments have confirmed a role for Epstein-Barr virus in the development of MS and, in particular, how a transcription factor of this virus drives the disease process.