# Deciphering the Role of Epstein-Barr Virus Molecular Mimicry and B cell Transformation in Multiple Sclerosis

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $586,186

## Abstract

PROJECT SUMMARY/ABSTRACT
Infection with Epstein-Barr Virus (EBV) has been epidemiologically demonstrated to be a pre-requisite for
developing multiple sclerosis (MS), as essentially 100% of MS patients become infected with EBV prior to MS
onset. We recently identified molecular mimicry between the EBV transcription factor EBNA1 and the glial cellular
adhesion molecule GlialCAM in 20 - 25% of MS patients, and this is likely a critical mechanism underlying the
development of MS in this subset of patients. This R01 will take our investigation of the role of EBV in mediating
the pathogenesis of MS to the next level, through: (i) analysis of dysregulated transcriptional pathways in EBV-
transformed B cells derived from MS patients, (ii) investigation of the ability of EBV-transformed B cells to
mediate autoreactive T cell activation, and (iii) characterization of molecular mimicry-related EBV and CNS
autoantibodies in MS. We will test the hypothesis that in MS, EBV activates B cells to circumvent B cell tolerance,
and thereby drive autoantibody production, autoreactive T cell activation, and MS pathology. We further
hypothesize that different reactivities to self-antigens, to EBV, and to molecular mimics are pathognomonic for
distinct MS disease subtypes with different HLA/genetic backgrounds and disease characteristics. Aim 1 will
analyze dysregulated transcriptional pathways in EBV+ B cells derived from MS vs. controls. Aim 2 will express
MS EBV+ B cell-encoded monoclonal antibodies and identify their EBV and CNS targets. Aim 3 will investigate
the ability of EBV-transformed B cells to mediate autoreactive T cell activation. Aim 4 will perform serologic
analysis to characterize molecular mimicry-related EBV and CNS autoantibodies in sera from large cohorts of
MS and comparator patients. Success of the proposed studies would elucidate the mechanisms by which EBV
causes MS, which would transform our understanding of MS and could lead to fundamental therapies.

## Key facts

- **NIH application ID:** 10758967
- **Project number:** 5R01AI173189-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Tobias Volker Lanz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $586,186
- **Award type:** 5
- **Project period:** 2023-01-03 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758967

## Citation

> US National Institutes of Health, RePORTER application 10758967, Deciphering the Role of Epstein-Barr Virus Molecular Mimicry and B cell Transformation in Multiple Sclerosis (5R01AI173189-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10758967. Licensed CC0.

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