Epstein–Barr virus and multiple sclerosis: lesson learned to develop better nonhuman primate models

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...

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Main Authors: Hai Duc Nguyen, Daesik Kim, Yong-Hee Kim, Erik Flemington, Gavin Giovannoni, Chung-Gyu Park, Woong-Ki Kim
Format: Article
Language:English
Published: Nature Publishing Group 2025-06-01
Series:Experimental and Molecular Medicine
Online Access:https://doi.org/10.1038/s12276-025-01482-5
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author Hai Duc Nguyen
Daesik Kim
Yong-Hee Kim
Erik Flemington
Gavin Giovannoni
Chung-Gyu Park
Woong-Ki Kim
author_facet Hai Duc Nguyen
Daesik Kim
Yong-Hee Kim
Erik Flemington
Gavin Giovannoni
Chung-Gyu Park
Woong-Ki Kim
author_sort Hai Duc Nguyen
collection DOAJ
description 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.
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spelling doaj-art-3bd6ccc717a5442a89b8e2e3b3f4dde22025-08-20T04:01:26ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-06-015761143115110.1038/s12276-025-01482-5Epstein–Barr virus and multiple sclerosis: lesson learned to develop better nonhuman primate modelsHai Duc Nguyen0Daesik Kim1Yong-Hee Kim2Erik Flemington3Gavin Giovannoni4Chung-Gyu Park5Woong-Ki Kim6Division of Microbiology, Tulane National Primate Research Center, Tulane UniversityTransplantation Research Institute, Seoul National UniversityTransplantation Research Institute, Seoul National UniversityDepartment of Pathology and Laboratory Medicine, Tulane University School of MedicineBlizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of LondonTransplantation Research Institute, Seoul National UniversityDivision of Microbiology, Tulane National Primate Research Center, Tulane UniversityAbstract 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.https://doi.org/10.1038/s12276-025-01482-5
spellingShingle Hai Duc Nguyen
Daesik Kim
Yong-Hee Kim
Erik Flemington
Gavin Giovannoni
Chung-Gyu Park
Woong-Ki Kim
Epstein–Barr virus and multiple sclerosis: lesson learned to develop better nonhuman primate models
Experimental and Molecular Medicine
title Epstein–Barr virus and multiple sclerosis: lesson learned to develop better nonhuman primate models
title_full Epstein–Barr virus and multiple sclerosis: lesson learned to develop better nonhuman primate models
title_fullStr Epstein–Barr virus and multiple sclerosis: lesson learned to develop better nonhuman primate models
title_full_unstemmed Epstein–Barr virus and multiple sclerosis: lesson learned to develop better nonhuman primate models
title_short Epstein–Barr virus and multiple sclerosis: lesson learned to develop better nonhuman primate models
title_sort epstein barr virus and multiple sclerosis lesson learned to develop better nonhuman primate models
url https://doi.org/10.1038/s12276-025-01482-5
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