Epstein-Barr Virus (EBV)-Specific Humoral Immune Responses in Health and Disease

Epstein-Barr virus (EBV) infection has been associated with an expanding range of acute inflammatory, malignant, and autoimmune disorders. Seroepidemiological studies, facilitated by the early identification of key immunodominant targets of the EBV-specific humoral response, have provided invaluable insights into pathogenicity and global prevalence and incidence of EBV infections. These studies have also identified distinct antibody signatures associated with both the acute and persistent phases of infection, as well as EBV-related disorders. Over time, research into the humoral immune response against EBV has progressed from traditional cell-based immunofluorescence methods to high-throughput multiplex assays utilizing recombinant proteins or synthetic peptides as substrates. These improvements have shifted the focus from individual immunodominant antigens to the entire EBV proteome, enhancing our understanding of antiviral antibody responses in both health and disease. Detailed analyses of antigenic epitopes have uncovered significant biochemical and sequence homology between viral and host proteins, providing a conceptual framework for understanding the development of autoimmune diseases by a phenomenon known as antigenic mimicry. Recently, research has shifted toward translating these immune response findings into therapeutic strategies aimed at inducing or restoring immunity in patients with EBV-associated disorders. This chapter seeks to provide a comprehensive overview of the humoral immune response to EBV in healthy virus carriers and patients with EBV-associated disorders, tracing developments from the discovery of the virus 60 years ago to the present day and offering a perspective on future directions.