The Epstein-Barr virus (EBV), a member of the herpesvirus family, silently infects the majority of the global population, often without detectable symptoms. While its presence frequently goes unnoticed, EBV harbors the potential to initiate severe diseases such as certain cancers and autoimmune disorders, including multiple sclerosis (MS). Recent groundbreaking research conducted by scientists at the German Cancer Research Center (DKFZ) and Heidelberg University Hospital has unveiled a critical mechanism through which EBV manipulates the immune system to its advantage, shedding new light on viral persistence and disease progression.
EBV was the first virus unequivocally linked to human cancer, a discovery dating back to the 1960s. However, the intricate molecular interplay that underlies its carcinogenic capacity remains elusive. The virus exhibits a remarkable tropism for B lymphocytes, a subset of immune cells, which are crucial not only in mounting immune responses but also represent the cell population from which EBV-induced cancers such as Burkitt’s lymphoma originate. Intriguingly, the role of EBV extends beyond oncogenesis, implicating these infected B cells in the etiology of autoimmune conditions like MS, where the immune system mistakenly targets and degrades the protective myelin sheath enveloping neurons.
A striking feature of EBV infection is its capacity to enter a lifelong latent state within host B cells. This latent reservoir means the virus can evade immune detection and persist indefinitely. Despite this dormancy, the virus is far from inactive; it modulates host cell functions, particularly the migratory behavior of infected B cells. Researchers led by Henri-Jacques Delecluse focused on this phenomenon and discovered that EBV-infected B cells acquire characteristics of “homing cells.” These are specialized immune cells capable of transiting from lymphatic vessels through the vascular endothelium to reach target tissues, a tightly regulated process essential for normal immune surveillance.
The novelty of the DKFZ and Heidelberg team’s findings lies in demonstrating that EBV hijacks this homing mechanism, subverting normal cytokine control to facilitate the spread of infected B cells throughout the host organism. This viral manipulation enhances the ability of these cells to traverse the endothelial barrier—a critical checkpoint consisting of tightly joined endothelial cells lining blood and lymph vessels. Such translocation is essential for immune cell trafficking but, when aberrantly induced by EBV, facilitates systemic dissemination of the virus.
Crucially, two viral proteins, EBNA2 and LMP1, have been identified as key drivers of this pathological migration. These proteins stimulate the production of pro-inflammatory cytokines such as CCL4, which are known mediators in inflammatory processes and are particularly relevant in MS pathogenesis. This pro-inflammatory environment not only promotes proliferation of infected B cells but also induces them to cross endothelial barriers—in essence enabling them to “swarm” into various tissues including the brain, where they may trigger or exacerbate autoimmune damage.
The research illuminates a molecular cascade whereby EBNA2 and LMP1 orchestrate chemotactic signaling activating receptors such as CCR1, which are intricately involved in leukocyte trafficking and have been implicated in MS. This receptor-ligand interaction modulates cytoskeletal dynamics and focal adhesion pathways, processes essential for cell motility and diapedesis (the passage of cells through the blood vessel wall). Importantly, the team demonstrated that EBV-induced migration depends on FAK (focal adhesion kinase)-dependent chemotaxis, providing a molecular target for intervention.
Translating these insights into therapeutic avenues, the researchers employed specific inhibitors targeting these pathways in animal models. These interventions successfully suppressed the migration of EBV-infected B cells and reduced their survival rates, effectively limiting viral dissemination within the body and, notably, to the central nervous system. This represents a pioneering step in deploying molecular inhibitors to prevent virus-fueled autoimmunity and tumorigenesis by physically constraining the mobility of infected immune cells.
The implications of these findings are profound. If such inhibitor-based approaches prove effective in humans, they could revolutionize treatment strategies for MS by preventing the infiltration of autoreactive B cells into neural tissue, potentially halting or ameliorating the destructive demyelinating processes characteristic of the disease. Furthermore, this research opens new research frontiers for targeting virus-driven cancers by limiting the invasive capabilities of tumor-associated B cells.
Given that more than 95 percent of adults over 50 years in Germany harbor EBV, with primary infections often asymptomatic in childhood and symptomatic in adults as Pfeiffer’s glandular fever, understanding the viral strategies to evade the immune system and promote dissemination is paramount. The persistent viral reservoir in B cells represents both a challenge and an opportunity for novel antiviral and immunomodulatory therapies aimed at controlling EBV’s pathogenic sequelae.
The study represents a critical convergence of virology, immunology, and neurobiology, elucidating the molecular underpinnings of EBV-induced alterations in immune cell behavior. It exemplifies how pathogens exploit host cellular machinery not only to ensure survival but also to propagate systemic infection and induce disease. Unraveling such viral-host interactions at a cellular and molecular level is instrumental for the development of next-generation therapeutics.
As the German Cancer Research Center continues to pioneer cancer and infection research, collaborations with leading clinical and translational institutes worldwide will be vital in advancing these discoveries from bench to bedside. This promising approach underscores the importance of interdisciplinary research in tackling complex diseases that lie at the intersection of infection, immunity, and chronic illness.
While further clinical studies are essential to validate these findings in human subjects, the DKFZ’s work marks a paradigm shift in understanding EBV’s role in autoimmune disease and cancer. The possibility of pharmacologically inhibiting EBV-induced B cell migration offers hope for millions affected by MS and EBV-associated malignancies, heralding a new era of targeted, molecularly informed therapies.
Subject of Research: Epstein-Barr virus (EBV) influences on immune cell migration and its implications in cancer and multiple sclerosis.
Article Title: Epstein-Barr virus induces aberrant B cell migration and diapedesis via FAK-dependent chemotaxis pathways.
News Publication Date: Not explicitly specified; inferred as 2025 based on publication.
Web References: 10.1038/s41467-025-59813-z
References: S. Delecluse et al. Nature Communications 2025
Keywords: Health and medicine, Epstein-Barr virus, B cell migration, autoimmune disease, multiple sclerosis, viral oncology, immune cell trafficking, cytokines, FAK signaling
Tags: B lymphocytes and EBVcarcinogenic properties of EBVEBV and autoimmune disordersEBV-induced diseasesEpstein-Barr virus infection mechanismsEpstein-Barr virus research findingsglobal prevalence of Epstein-Barr virusherpesvirus family infectionsimmune system manipulation by EBVlinks between EBV and multiple sclerosisrole of EBV in cancerviral persistence in the body
