Publications

Research Papers

Posted on November 4, 2025  •  5 minutes  • 1058 words

BEHIND-MS Research publications

• EBV infection and HLA-DR15 jointly drive multiple sclerosis by myelin peptide presentation

Wang, J., Magliozzi, R., et al. EBV infection and HLA-DR15 jointly drive multiple sclerosis by myelin peptide presentation Cell, v. 189, iss. 2, (2026)

This publication shows that EBV infection alters the transcriptome of B cells, which leads to presentation of MBP peptides on HLA-DR15 molecules. MBP peptide-specific CD4 + T cells are found in the peripheral immune compartment and CNS, where they recognize the same MBP peptides on HLA-DR15 molecules. Roberta Magliozzi from the BEHIND-MS consortium contributed to this publication by performing EBV-detection analyses in the meninges and perivascular vessels of the examined MS brain tissue.

• EBV Early Lytic Antigens, EBNA2 and PDL-1, in Progressive Multiple Sclerosis Brain: A Coordinated Contribution to Viral Immune Evasion

Serafini, B. et al. EBV Early Lytic Antigens, EBNA2 , Int. J. Mol. Sci. (2026)

Epstein-Barr virus (EBV) infection shows the strongest causative association with multiple sclerosis (MS), but its contribution to disease progression and the mechanisms allowing for viral persistence in the MS brain are still elusive. Studies in post-mortem MS brain tissue indicate an ongoing yet ineffective antiviral immune reaction in advanced stages of the disease. EBV has evolved strategies to evade immune recognition and clearance by the host immune system during both the latency and lytic phase of its life cycle. Recent evidence demonstrates that cells expressing EBV latent membrane protein (LMP) 2A exploit the PD-1/PDL1 inhibitory immune checkpoint to escape immune surveillance and maintain a persistent latent infection in the MS brain. This study investigated whether the virus also utilizes this inhibitory mechanism during other phases of the viral life cycle. By using multiple immunostainings on highly inflamed MS brain tissues containing meningeal tertiary lymphoid structures (TLSs), we analyzed PD-L1 expression on EBV-infected cells expressing EBNA2, five EBV lytic gene products, BZLF1, BHRF1, BMRF1, BALF2, and gp350/220, as well as on follicular dendritic cells within the TLSs. This is the first study describing in secondary progressive MS brain tissue the expression and the cellular and tissue distribution of PD-L1 on EBV-infected cells being in different stages of the viral life cycle, and confirms the meningeal TLSs as immune-permissive habitats favoring the maintenance of an intracerebral EBV reservoir.

• Recent advances in animal models of lymphomagenesis caused by human γ-herpesviruses

Münz, C. Recent advances in animal models of lymphomagenesis caused by human γ-herpesviruses , Current Opinion in Virology (2025)

The two human γ-herpesviruses Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) cause around 2–3% of all cancers in man. Their exclusive tropism for humans and associated lack of small animal models has impeded the dissection of individual viral gene contributions to tumor formation and of protection by distinct immune responses that are observed in virus carriers. Mice with reconstituted human immune systems (humanized mice) now offer the possibility to study these questions and to develop adoptive antibody and T cell transfers against EBV- and KSHV-associated pathologies. Based on such protective immune responses, vaccine candidates can then be developed to prophylactically and therapeutically induce immune control, similar to the one that avoids virus-associated pathologies in the vast majority of infected individuals.

• Epstein–Barr virus pathogenesis and emerging control strategies

Münz, C. Epstein–Barr virus pathogenesis and emerging control strategies Nat Rev Microbiol (2025).

Sixty years after its discovery as the first human tumour virus, Epstein–Barr virus (EBV)-specific therapies and vaccines have entered clinical trials. These might not only be applicable for EBV-associated malignancies, where the virus was originally discovered, but also to immunopathologies, including the autoimmune disease multiple sclerosis, which might be triggered in susceptible individuals by primary EBV infection. This Review discusses the surprisingly large spectrum of diseases that EBV seems to cause, as well as which of these might be treated by the therapeutic approaches that are currently being developed or are already clinically applied. New pharmacological inhibitors, antibody therapies, adoptive T cell therapies and active vaccinations are beginning to offer possibilities to target the various EBV infection programmes that are associated with different diseases. These novel developments might allow us to specifically target EBV rather than its host cells in virus-associated pathologies.

• Epstein–Barr virus induces aberrant B cell migration and diapedesis via FAK-dependent chemotaxis pathways

Delecluse, S., Baccianti, F., Zala, M., et al. & Delecluse, H.J. Epstein–Barr virus induces aberrant B cell migration and diapedesis via FAK-dependent chemotaxis pathways Nat Commun (2025).

Many people are infected with the Epstein-Barr virus (EBV), and most are unaware of it. However, EBV can sometimes cause cancer, and this pathogen also appears to play an important role in multiple sclerosis and other autoimmune diseases. Researchers at the German Cancer Research Center (DKFZ) and the Kidney Center at Heidelberg University Hospital have discovered that EBV increases the ability of infected immune cells to migrate. In this way, the pathogen promotes its spread in the body – a discovery that may have therapeutic implications.

• Altered EBV specific immune control in multiple sclerosis

Münz, C., Altered EBV specific immune control in multiple sclerosis Journal of Neuroimmunology (2024).

This review discusses the epidemiological evidence that EBV infection starts the pathogenic process that leads to multiple sclerosis (MS). It also outlines possible mechanisms by which EBV might trigger and sustain the underlying disease process.

• EBV-specific T-cell immunity: relevance for multiple sclerosis

Behrens M, Comabella M, Lünemann JD. EBV-specific T-cell immunity: relevance for multiple sclerosis Front Immunol. (2024)

While the infection with Epstein-Barr virus infection has been shown to be a consistent risk factor for the development of multiple sclerosis in recent years, the biological basis of this association remains incompletely understood. This review presents the most up to date research in the field, specifically regarding the role of T and B cells, and provides future avenues for further research elucidating the role of EBV in MS.

• Increased EBNA1-specific antibody response in primary-progressive multiple sclerosis

Comabella M. et al. & Lünemann JD. Increased EBNA1-specific antibody response in primary-progressive multiple sclerosis J Neurol. (2024)

While the association between EBA and MS has been primarily studied in most prevalent form of MS (relapse-onset MS, RMS), this study examines immune responses to ubiquitous viruses, including EBV, in patients with primary-progressive multiple sclerosis (PPMS). Immune responses to EBV were increased in PPMS patients compared to healthy controls, but not to other ubiquitous viruses tested, suggesting a connection between an altered response to EBV and the development of PPMS/RMS.