Epstein-Barr virus and multiple sclerosis: lesson learned to develop better nonhuman primate models
Hai Duc Nguyen1, Daesik Kim2, Yong-Hee Kim2
1Division of Microbiology, Tulane National Primate Research Center, Tulane University, Covington, LA, USA.
Abstract:
Multiple sclerosis (MS) is a chronic autoimmune disorder with a complex etiology, and Epstein-Barr virus (EBV) is considered the leading cause. While understanding the role of EBV infection in the pathogenesis of MS in human subjects is crucial, animal models, particularly nonhuman primates (NHPs), would provide an ideal controlled environment for testing EBV hypotheses and identifying potential therapeutic targets. Here in this Review we address clinically relevant questions regarding the link between EBV infection and MS to inform the development and refinement of virally induced NHP models. We focus on integrating known EBV-related risk factors for MS, including age at infection, infectious mononucleosis, genetic predispositions such as the human leukocyte antigen (HLA)-DR15 haplotype, sex-specific susceptibility, low vitamin D levels and CD8+ T cell deficiency. We also explore the application of these risk factors in model development, investigate why most EBV-infected individuals do not develop MS and propose potential disease-modifying therapeutic options and vaccines. Integrating these approaches into NHP models will improve our understanding of MS pathogenesis and guide the development of targeted strategies for disease management and prevention. We propose to develop a refined EBV infection NHP model of MS coupled with CD8+ cell depletion and other inclusion and exclusion criteria.
Insights
Epstein-Barr virus (EBV) is linked to multiple sclerosis (MS). This review explores EBV risk factors and proposes nonhuman primate (NHP) models to study MS pathogenesis and develop therapies.
Area of Science:
- Neuroimmunology
- Virology
- Translational Medicine
Background:
- Multiple sclerosis (MS) is a chronic autoimmune disease with a complex cause, where Epstein-Barr virus (EBV) is a primary suspect.
- Understanding EBV's role in MS pathogenesis is vital, but human studies are limited.
- Nonhuman primate (NHP) models offer a controlled environment to test EBV-MS hypotheses and identify therapeutic targets.
Purpose of the Study:
- To address clinically relevant questions about the EBV-MS connection.
- To inform the development and refinement of EBV-induced NHP models for MS research.
- To integrate known EBV-related risk factors into NHP model design.
Main Methods:
- Review of existing literature on EBV infection and MS.
- Analysis of EBV-related risk factors: age at infection, infectious mononucleosis, HLA-DR15, sex, vitamin D, and CD8+ T cell deficiency.
- Proposal for developing a refined EBV infection NHP model of MS with CD8+ cell depletion.
Main Results:
- Identified key EBV-related risk factors for MS.
- Explored the application of these risk factors in NHP model development.
- Investigated reasons why most EBV-infected individuals do not develop MS.
- Proposed potential disease-modifying therapies and vaccines.
Conclusions:
- Integrating EBV risk factors into NHP models will enhance understanding of MS pathogenesis.
- Refined NHP models are crucial for guiding targeted strategies in MS management and prevention.
- A proposed NHP model incorporating EBV infection and CD8+ cell depletion could advance MS research.
