Elucidating the Biological Mechanisms Underlying the Association Between Epstein-Barr Virus and Multiple Sclerosis
Abstract
Infection with the Epstein-Barr virus (EBV) is likely the leading cause of multiple sclerosis (MS). In a recently published study, infection with EBV was associated with a 32-fold increased risk of MS, and among the 801 patients included in the study, only one was not infected with the virus before developing MS. While these findings are intriguing, it is not yet known how EBV is causing the disease. Some studies have found that EBV peptides, which are parts of proteins, resemble peptides in the brain and other parts of the central nervous system, which could cause the immune system to accidentally attack important structures in the brain, such as healthy nerve cells, when trying to eliminate the virus, a theory called molecular mimicry. Still, it remains unclear whether this can fully explain why EBV is causing MS. In addition to causing the disease, EBV could also affect disease activity and symptoms in MS patients. Recently, a study proposed that EBV may play a similar role in MS as gluten plays in celiac disease and that by targeting EBV, safer and more effective treatments than those currently available could be developed. Thus, more knowledge about the mechanisms by which EBV is causing MS could have major implications both for the prevention and treatment of MS. Therefore, we propose to conduct a comprehensive study that will characterize the immune response to EBV in detail and evaluate whether molecular mimicry plays an important role for the development of the disease. Further, we aim to determine whether we can identify individuals who are at high risk of developing MS based on their immune response to EBV shortly after being infected with the virus, which could have implications for early detection and diagnosis of MS. The aims of this project are to (1) investigate whether an infection with EBV affects the immune response to other viruses and bacteria, (2) to evaluate whether human peptides resembling EBV peptides in previous studies increase the risk of MS, and (3) to conduct analyses of several thousand human peptides and examine whether there is an immune response to other, currently unknown, peptides that could help to explain how EBV is causing MS, and whether the immune response to these peptides can be used to identify those at high risk of later developing MS. The first aim will evaluate whether EBV, a virus that co-evolved with humans for thousands of years, in addition to causing diseases such as MS and specific types of cancer, also could play an advantageous role for the immune system, for example by strengthening immunity against other viruses and bacteria. This would be important to determine for the implementation of an EBV vaccine in the general population. The second aim will validate whether serum levels of human peptides previously suggested to cross-react (by molecular mimicry) with EBV are associated with the risk of MS when measured years before the first symptoms of the disease. In the third aim, we will explore whether other, currently unknown, human peptides cross-react with EBV and are associated with MS risk. Results from the two last aims have implications for the development of more targeted MS treatment, identification of biomarkers for interventions targeting EBV, and for early detection and diagnosis of MS patients. The proposed study will be conducted using clinical data and serum samples from active-duty military personnel. While being on active duty, serum specimens are collected from Service Members on average every 2 years, and these samples are stored in the Department of Defense Serum Repository. Currently, this repository contains over 60 million archived serum specimens from over 11 million individuals. For the past 20 years, we have identified individuals who developed MS while being on active duty. The proposed study will include samples that have already been collected during our previous work on MS in this population. In these serum samples, w
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310871
Entities
People
- Alberto Ascherio
Organizations
- President and Fellows of Harvard College
- United States Army