Epstein–Barr Virus (EBV, HHV‑4) is an enveloped double‑stranded DNA virus of the Gammaherpesvirinae subfamily that infects B lymphocytes and oropharyngeal epithelial cells. It is best known for causing infectious mononucleosis and is implicated in several lymphoid and epithelial malignancies.
Molecular Biology and Latency
EBV gains entry into B cells by binding its major envelope glycoprotein gp350/220 to the complement receptor CD21 (CR2) and using gp42 to engage HLA class II molecules. It can also infect epithelial cells through integrin interactions. After fusion and delivery of the 172 kilobase genome to the nucleus, EBV replicates either lytically or enters latency. Lytic replication involves sequential expression of immediate early, early and late genes, leading to production of virions that are shed in saliva. During latency the viral genome persists as a circular episome within the host nucleus and expresses a limited set of latent genes. Three latency programs (types I, II and III) are characterized by specific patterns of Epstein‑Barr nuclear antigens (EBNA1, EBNA2, EBNA3A–3C) and latent membrane proteins (LMP1, LMP2A/B) that drive B cell survival and proliferation. Small noncoding RNAs (EBERs) and viral microRNAs modulate host immunity. EBV establishes a lifelong reservoir in resting memory B cells and periodically reactivates to infect new hosts.
Clinical Manifestations and Oncogenicity
Primary EBV infection acquired through saliva in adolescence or adulthood often results in infectious mononucleosis, characterized by fever, pharyngitis, cervical lymphadenopathy, fatigue and atypical lymphocytosis. Splenomegaly poses a risk of rupture, so strenuous activities should be avoided. In contrast, childhood infection is frequently asymptomatic. EBV is oncogenic: it contributes to endemic Burkitt lymphoma in malaria‑endemic regions, nasopharyngeal carcinoma in Southeast Asia, Hodgkin lymphoma and some gastric carcinomas. Immunocompromised patients may develop post‑transplant lymphoproliferative disease due to uncontrolled proliferation of latently infected B cells. The virus has also been linked to autoimmune disorders such as multiple sclerosis. Diagnosis relies on heterophile antibody testing or EBV‑specific serology, and treatment of mononucleosis is supportive; antivirals have limited effect. Management of EBV‑associated cancers involves chemotherapy and immunotherapy. There is currently no approved vaccine, though several candidates are under development.
EBV infects most humans worldwide and exemplifies the complex interplay between viral latency, immunity and oncogenesis. Understanding its biology has provided insights into B‑cell transformation and immune evasion but effective prevention and targeted therapies remain areas of ongoing research.
Related Terms: infectious mononucleosis, Burkitt lymphoma, nasopharyngeal carcinoma, latency, B lymphocyte