From infection to immune exhaustion: The Epstein-Barr virus and its contribution to Immunosenescence. (2025)

Epstein-Barr virus (EBV), a common herpesvirus, is linked to chronic infections and malignancies like lymphomas and nasopharyngeal carcinoma. EBV's evasion of immune surveillance and induction of immune dysfunction are critical for disease progression. This review explores how EBV drives immune exhaustion and immunosenescence, focusing on its effects on T and NK cells. Chronic EBV infection causes persistent antigenic stimulation and upregulation of immune checkpoint molecules (PD-1, LAG-3, TIM-3, CTLA-4), leading to reduced T and NK cell proliferation, cytokine secretion, and cytotoxicity-hallmarks of immune exhaustion. EBV also modulates cytokines (IL-10, IL-18, IL-6, TNF-alpha), further disrupting immune surveillance and promoting tumor growth within the tumor microenvironment. Furtherm