Epstein-Barr virus associated diseases: Immune alterations and targeted approaches

Epstein-Barr virus (EBV) is a ubiquitous human γ-herpesvirus associated with a wide spectrum of diseases, ranging from autoimmune diseases to malignancies. Recognized as the first human oncogenic virus, multifaceted pathogenesis of EBV-associated diseases has been extensively explored. However, recent evidence suggests that EBV modulates immune cell function to influence the initiation and progression of associated diseases. Expressing a diverse repertoire of viral RNAs and proteins, EBV not only maintains latency with multiple immune evasion mechanisms, but also modulates host cell biology and sculpts a disease-specific immune microenvironment through dynamic interactions with various immune cells like T cells, B cells, macrophages, natural killer cells, and dendritic cells. Correspondingly, an increasing number of immunotherapies targeted T cells, B cells and virus itself have been developed for improved efficacy, including monoclonal antibodies, chimeric antigen receptor T cell (CAR-T) therapy, vaccines, and lytic induction strategies. In this review, regulatory roles of EBV in modulating the immune microenvironment in different context of disease and emerging therapeutic strategies targeted the underlying molecular mechanisms have been systematically discussed. Future research should aim to elucidate the precise molecular pathways involved, identify key therapeutic targets, characterize intra- and inter-tumor heterogeneity, and develop virus-directed strategies to fundamentally counteract EBV-induced immunopathogenic effects.