Epstein-Barr virus (EBV) is a common herpesvirus that primarily infects B cells, a type of white blood cell essential for immune function. Research on EBV and B cell therapy is a rapidly evolving field that explores how EBV infects and manipulates B cells, how this interaction contributes to diseases such as multiple sclerosis (MS) and certain lymphomas, and how therapies targeting B cells can influence EBV-related conditions.
EBV infects naïve B cells by binding to specific receptors on their surface, initiating a complex process that allows the virus to enter and establish a lifelong latent infection. During this latent phase, EBV expresses certain viral proteins, notably EBNA2 and LMP1, which hijack the normal functions of B cells. These proteins stimulate the production of inflammatory molecules like CCL4, creating an environment that promotes the survival, proliferation, and migration of infected B cells throughout the body. This migration involves crossing endothelial barriers—tight layers of cells lining blood and lymph vessels—allowing EBV-infected B cells to disseminate systemically, including into the brain. This process is significant because it may trigger or worsen autoimmune diseases such as MS by promoting inflammation and immune system dysregulation in sensitive tissues.
The molecular mechanisms behind this migration involve chemotactic signaling pathways, where viral proteins activate receptors like CCR1 on B cells. This activation modulates the cytoskeleton and focal adhesion pathways, which are critical for cell movement and the ability to pass through blood vessel walls. A key molecule in this process is focal adhesion kinase (FAK), which EBV exploits to enhance the motility of infected B cells. Targeting FAK-dependent chemotaxis is being investigated as a potential therapeutic approach to limit EBV spread and its pathological effects.
In addition to its role in autoimmune diseases, EBV-driven B cell proliferation can lead to malignancies such as post-transplant lymphoproliferative disorder (PTLD) and diffuse large B-cell lymphoma, especially in immunosuppressed individuals. Chronic immunosuppression, for example after organ transplantation, impairs the immune system’s ability to control EBV, allowing unchecked proliferation of infected B cells. Treatments like rituximab, which depletes B cells, are used to manage these conditions but are not always fully effective, highlighting the need for better understanding and novel therapies.
B cell therapies, particularly those that deplete B cells, have shown promise in diseases linked to EBV. Many disease-modifying therapies for MS work by targeting B cells, either directly or indirectly affecting EBV biology. This supports the hypothesis that ongoing EBV infection or reactivation contributes to the inflammatory activity seen in MS. Interestingly, epidemiological data show that people with HIV on antiretroviral therapy, which can also suppress EBV, have a lower risk of developing MS, suggesting that antiviral strategies targeting EBV might be beneficial in autoimmune diseases.
The relationship between EBV and autoimmunity is complex. EBV can disrupt B cell regulatory checkpoints, leading to the development of autoreactive plasma cells that produce harmful antibodies. Viral reactivation, such as after infections like COVID-19, may exacerbate this process by promoting inflammatory responses and immune dysregulation. Mechanisms proposed include molecular mimicry (where viral proteins resemble self-antigens), bystander activation of immune cells, and persistent viral infection, all contributing to autoimmune disease flares and chronic symptoms.
Current research is focused on better understanding how EBV manipulates B cells at the molecular level, how this contributes to disease, and how therapies can be designed to specifically target EBV-infected B cells or the pathways they exploit. This includes developing drugs that inhibit viral proteins, block chemotactic signaling, or enhance immune control of EBV. Re-evaluating existing B cell-targeting therapies for their effects on EBV is also a priority, as is exploring an
