The Epstein-Barr virus (EBV) is a common and usually innocuous virus that infects up to 95% of the world’s population. Typically transmitted through saliva, EBV remains in the immune system for life. In individuals with certain genetic risk factors it may later trigger problems with how the immune system behaves. While infection is often asymptomatic, a small proportion of individuals develop glandular fever.
However, growing evidence suggests that the virus may play a much more significant role in disease pathogenesis. Research has shown that the vast majority of people who develop the complex autoimmune and neurodegenerative condition multiple sclerosis (MS) have previously been infected with EBV, indicating EBV as a key contributor to disease development.
Over the past decade, EBV-MS research has expanded rapidly, spanning large population studies, genomics, immunology and clinical trials across multiple continents.
In Australia, more than 37,700 people are living with MS.
Researchers around the world are investigating the connection between EBV and MS, examining whether the development of the disease may be linked to specific genetic variations, or strains, of EBV.
Dr Yuan Zhou is the lead investigator of a major Australian project (funded by MRFF) within the Australian Consortium for EBV Research in MS (ACE-MS). Dr Zhou is based at the Menzies Institute for Medical Research at the University of Tasmania.
Coordinated by MS Australia, the ACE-MS consortium attracted participation from 20 research groups across Australia and brought together 11 major EBV projects with >$10M in funding for EBV research.
Dr Zhou’s team is working to establish whether particular EBV genetic variants are associated with an increased risk of developing MS, with the aim of developing a risk scoring approach.
Building Australian EBV reference genomes
As part of the project, a library of EBV reference genomes specifically relevant to the Australian population will be created. This resource could help inform the design of future EBV vaccines.
“The development of a country‑specific library of EBV reference genomes is significant because EBV is not genetically uniform across populations. Its variation is shaped by geography, ethnicity and local transmission patterns,” explains Dr Zhou.
A nationally representative EBV genome library may help identify high‑risk viral variants, enable more accurate links between EBV strain types and disease outcomes, and support the development of targeted prevention and screening strategies
Dr Zhou’s team, in collaboration with researchers from QIMR Berghofer Medical Research Institute and the University of Queensland, is working closely with interdisciplinary research teams across Asia and Europe to improve MS diagnosis, treatment and prevention.
Key international collaborators include the Genome Institute of Singapore and partners involved in the European EBV-MS Consortium, funded through the Horizon Europe research program and comprising >10 institutions across different European countries such as the Netherlands, Switzerland and Spain.
“Currently, by the time MS is diagnosed, there is already damage occurring in the brain. It is hard to turn back the clock,” says Dr Zhou.
“If we are able to show that MS development is influenced by specific EBV strains, there may be future opportunities to prevent the disease through early or preventative interventions.”
Part of a global research effort
Dr Zhou says these national and international collaborations are contributing to a growing global effort to better understand the role of EBV in MS and related conditions.
Genomic studies form one part of a much broader body of research into EBV and MS, alongside work on EBV‑specific T‑cell therapies and clinical trials investigating their use in people with MS.
“The rate of MS continues to grow, and there is presently no cure. While there are treatments that can help manage the disease, they cannot prevent disability from progressing,” Dr Zhou says.
“Collectively, researchers are trying to make significant inroads towards improving outcomes for people with MS.”
“The beauty of this work is that if we are on the right path, there is great potential to develop a vaccine that could benefit many people.”
Evidence from the US
A major study published in Science followed more than 10 million US military personnel and found compelling evidence that infection with Epstein-Barr virus is a trigger for most cases of multiple sclerosis.
Of the 801 individuals who developed MS during the study period, all but one had tested positive for EBV before their MS symptoms began. The findings suggest EBV is the strongest known risk factor for MS, increasing the risk of developing the disease by more than 30‑fold following infection.




