Shadows of Epstein-Barr Decoding the Silent Virus

AbstractEpstein-Barr virus (EBV), a double-stranded DNA virus belonging to the Herpesviridae family, infects over 95% of the global adult population, establishing lifelong latency primarily in B lymphocytes. Primary infections usually occur during childhood oradolescence, often presenting asymptomatically or as infectious mononucleosis (IM), which includes symptoms such as fever,pharyngitis, lymphadenopathy, and splenomegaly. EBV is associated with various malignancies, including Burkitt lymphoma,Hodgkin lymphoma, nasopharyngeal carcinoma, and gastric carcinoma, as well as lymphoproliferative disorders inimmunocompromised individuals due to its oncogenic potential. Recent epidemiological studies (2023–2025) have uncovered regional variations in infection patterns and suggested links to autoimmune diseases like multiple sclerosis, possibly through mechanisms of molecular mimicry and immune dysregulation. Pathogenetically, EBV employs latent membrane proteins (LMP1/2) and Epstein-Barr nuclear antigens (EBNAs) to disrupt cellular signaling pathways such as NF-κB, PI3K/AKT, and JAK/STAT. This disruption promotes cell proliferation, evasion of apoptosis, and immune escape. Advancements in next-generation sequencing have revealed the genotypic diversity of EBV, which can influence disease outcomes. In terms of therapy, while antiviral agents like acyclovir show limited efficacy against latent infections, emerging strategies—including EBV-specific cytotoxic T-cell therapies, monoclonal antibodies targeting viral glycoproteins (e.g., gp350), and prophylactic vaccines currently in clinical trials-hold promise for addressing EBV-related diseases. This review consolidates recent insights into EBV's interactions at both micro and macro levels, highlighting the necessity for integrated surveillance and targeted interventions to reduce the global burden of EBV-associatedpathologies