Epstein-Barr Virus and Multiple Sclerosis: A Convoluted Interaction and the Opportunity to Unravel Predictive Biomarkers
Since the early 1980s, Epstein-Barr virus (EBV) infection has been described as one of the main risk factors for developing multiple sclerosis (MS), and recently, new epidemiological evidence has reinforced this premise. EBV seroconversion precedes almost 99% of the new cases of MS and likely predat...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/8/7407 |
| _version_ | 1797605089276329984 |
|---|---|
| author | Oscar-Danilo Ortega-Hernandez Eva M. Martínez-Cáceres Silvia Presas-Rodríguez Cristina Ramo-Tello |
| author_facet | Oscar-Danilo Ortega-Hernandez Eva M. Martínez-Cáceres Silvia Presas-Rodríguez Cristina Ramo-Tello |
| author_sort | Oscar-Danilo Ortega-Hernandez |
| collection | DOAJ |
| description | Since the early 1980s, Epstein-Barr virus (EBV) infection has been described as one of the main risk factors for developing multiple sclerosis (MS), and recently, new epidemiological evidence has reinforced this premise. EBV seroconversion precedes almost 99% of the new cases of MS and likely predates the first clinical symptoms. The molecular mechanisms of this association are complex and may involve different immunological routes, perhaps all running in parallel (i.e., molecular mimicry, the bystander damage theory, abnormal cytokine networks, and coinfection of EBV with retroviruses, among others). However, despite the large amount of evidence available on these topics, the ultimate role of EBV in the pathogenesis of MS is not fully understood. For instance, it is unclear why after EBV infection some individuals develop MS while others evolve to lymphoproliferative disorders or systemic autoimmune diseases. In this regard, recent studies suggest that the virus may exert epigenetic control over MS susceptibility genes by means of specific virulence factors. Such genetic manipulation has been described in virally-infected memory B cells from patients with MS and are thought to be the main source of autoreactive immune responses. Yet, the role of EBV infection in the natural history of MS and in the initiation of neurodegeneration is even less clear. In this narrative review, we will discuss the available evidence on these topics and the possibility of harnessing such immunological alterations to uncover predictive biomarkers for the onset of MS and perhaps facilitate prognostication of the clinical course. |
| first_indexed | 2024-03-11T04:56:13Z |
| format | Article |
| id | doaj.art-84702f278bd04405be95c42d73736923 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:56:13Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-84702f278bd04405be95c42d737369232023-11-17T19:39:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248740710.3390/ijms24087407Epstein-Barr Virus and Multiple Sclerosis: A Convoluted Interaction and the Opportunity to Unravel Predictive BiomarkersOscar-Danilo Ortega-Hernandez0Eva M. Martínez-Cáceres1Silvia Presas-Rodríguez2Cristina Ramo-Tello3Multiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol-IGTP, 08916 Badalona, SpainDepartment of Immunology, Hospital Universitari Germans Trias i Pujol-IGTP, Universitat Autònoma de Barcelona, 08916 Badalona, SpainMultiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol-IGTP, 08916 Badalona, SpainMultiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol-IGTP, 08916 Badalona, SpainSince the early 1980s, Epstein-Barr virus (EBV) infection has been described as one of the main risk factors for developing multiple sclerosis (MS), and recently, new epidemiological evidence has reinforced this premise. EBV seroconversion precedes almost 99% of the new cases of MS and likely predates the first clinical symptoms. The molecular mechanisms of this association are complex and may involve different immunological routes, perhaps all running in parallel (i.e., molecular mimicry, the bystander damage theory, abnormal cytokine networks, and coinfection of EBV with retroviruses, among others). However, despite the large amount of evidence available on these topics, the ultimate role of EBV in the pathogenesis of MS is not fully understood. For instance, it is unclear why after EBV infection some individuals develop MS while others evolve to lymphoproliferative disorders or systemic autoimmune diseases. In this regard, recent studies suggest that the virus may exert epigenetic control over MS susceptibility genes by means of specific virulence factors. Such genetic manipulation has been described in virally-infected memory B cells from patients with MS and are thought to be the main source of autoreactive immune responses. Yet, the role of EBV infection in the natural history of MS and in the initiation of neurodegeneration is even less clear. In this narrative review, we will discuss the available evidence on these topics and the possibility of harnessing such immunological alterations to uncover predictive biomarkers for the onset of MS and perhaps facilitate prognostication of the clinical course.https://www.mdpi.com/1422-0067/24/8/7407acute infectious mononucleosisB cellschronic EBV infectionEpstein Barr-VirusEBV latency programsgenomic studies |
| spellingShingle | Oscar-Danilo Ortega-Hernandez Eva M. Martínez-Cáceres Silvia Presas-Rodríguez Cristina Ramo-Tello Epstein-Barr Virus and Multiple Sclerosis: A Convoluted Interaction and the Opportunity to Unravel Predictive Biomarkers International Journal of Molecular Sciences acute infectious mononucleosis B cells chronic EBV infection Epstein Barr-Virus EBV latency programs genomic studies |
| title | Epstein-Barr Virus and Multiple Sclerosis: A Convoluted Interaction and the Opportunity to Unravel Predictive Biomarkers |
| title_full | Epstein-Barr Virus and Multiple Sclerosis: A Convoluted Interaction and the Opportunity to Unravel Predictive Biomarkers |
| title_fullStr | Epstein-Barr Virus and Multiple Sclerosis: A Convoluted Interaction and the Opportunity to Unravel Predictive Biomarkers |
| title_full_unstemmed | Epstein-Barr Virus and Multiple Sclerosis: A Convoluted Interaction and the Opportunity to Unravel Predictive Biomarkers |
| title_short | Epstein-Barr Virus and Multiple Sclerosis: A Convoluted Interaction and the Opportunity to Unravel Predictive Biomarkers |
| title_sort | epstein barr virus and multiple sclerosis a convoluted interaction and the opportunity to unravel predictive biomarkers |
| topic | acute infectious mononucleosis B cells chronic EBV infection Epstein Barr-Virus EBV latency programs genomic studies |
| url | https://www.mdpi.com/1422-0067/24/8/7407 |
| work_keys_str_mv | AT oscardaniloortegahernandez epsteinbarrvirusandmultiplesclerosisaconvolutedinteractionandtheopportunitytounravelpredictivebiomarkers AT evammartinezcaceres epsteinbarrvirusandmultiplesclerosisaconvolutedinteractionandtheopportunitytounravelpredictivebiomarkers AT silviapresasrodriguez epsteinbarrvirusandmultiplesclerosisaconvolutedinteractionandtheopportunitytounravelpredictivebiomarkers AT cristinaramotello epsteinbarrvirusandmultiplesclerosisaconvolutedinteractionandtheopportunitytounravelpredictivebiomarkers |