Related Experiment Video
Updated: May 11, 2025
Separation of Immune Cell Subpopulations in Peripheral Blood Samples from Children with Infectious Mononucleosis
Published on: September 7, 2022
Exploring the role of EBV in multiple sclerosis pathogenesis through EBV interactome
Chiara Ballerini1, Roberta Amoriello2, Olfa Maghrebi2
1Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
Background:
Epstein-Barr virus (EBV) is a known risk factor for multiple sclerosis (MS), even though the underlying molecular mechanisms are unclear and engage multiple immune pathways. Furthermore, the ultimate role of EBV in MS pathogenesis is still elusive. In contrast, Cytomegalovirus (CMV) has been identified as a protective factor for MS.
Objectives:
This study aims to identify MS-associated genes that overlap with EBV interactome and to examine their expression in immune and glial cell subtypes.
Methods:
We used P-HIPSTer, GWAS, and the Human Protein Atlas (HPA) to derive data on the EBV interactome, MS-associated genes and single-cell gene expression in immune and glial cells. The geneOverlap and dplyr R packages identified overlapping genes. A similar analysis was done for CMV and Adenovirus as negative control. Metascape and GTEx analyzed biological pathways and brain-level gene expression; transcriptomic analysis was performed on glial cells and peripheral blood in MS and controls. All the analyses performed in this study were generated using publicly available data sets.
Results:
We identified a "core" group of 21 genes shared across EBV interactome, MS genes, and immune and glial cells (p<0.001). Pathway analysis revealed expected associations, such as immune system activation, and unforeseen results, like the prolactin signaling pathway. BCL2 in astrocytes, MINK1 in microglia were significantly upregulated while AHI1 was downregulated in MS compared to controls.
Conclusions:
Our findings offer novel insights into EBV and CMV interaction with immune and glial cells in MS, that may shed light on mechanisms involved in disease pathophysiology.
Insights
Epstein-Barr virus (EBV) is linked to multiple sclerosis (MS) risk. This study identified shared genes between EBV, MS, and immune cells, revealing potential disease mechanisms. Cytomegalovirus (CMV) showed a protective association.
Area of Science:
- Neuroimmunology
- Virology
- Genetics
Background:
- Epstein-Barr virus (EBV) is a known risk factor for multiple sclerosis (MS), but its precise role in pathogenesis remains unclear.
- Cytomegalovirus (CMV) exhibits a protective association with MS, contrasting with EBV's risk factor status.
- Understanding the molecular interplay between viruses and the immune system is crucial for elucidating MS pathophysiology.
Purpose of the Study:
- To identify genes associated with MS that overlap with the Epstein-Barr virus (EBV) interactome.
- To investigate the expression patterns of these overlapping genes in various immune and glial cell subtypes.
- To explore the potential roles of EBV and CMV in MS pathogenesis.
Main Methods:
- Utilized P-HIPSTer, Genome-Wide Association Studies (GWAS), and the Human Protein Atlas (HPA) for data acquisition.
- Employed R packages (geneOverlap, dplyr) to identify overlapping genes between EBV interactome and MS-associated genes.
- Conducted pathway analysis (Metascape) and gene expression analysis (GTEx, transcriptomics) on publicly available datasets.
Main Results:
- Identified a core set of 21 genes significantly shared across EBV interactome, MS genes, and immune/glial cells.
- Pathway analysis highlighted immune system activation and the prolactin signaling pathway.
- Observed differential gene expression in specific cell types: BCL2 and MINK1 upregulated in astrocytes and microglia, respectively, while AHI1 was downregulated in MS.
Conclusions:
- The study provides novel insights into the interactions between EBV, CMV, and host cells in the context of MS.
- Findings may illuminate previously unknown molecular mechanisms contributing to MS development and progression.
- Highlights the potential of targeting viral-host interactions for future therapeutic strategies in MS.
