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Epstein-Barr virus (EBV) asymptomatically infects over 95% of the global population, and poses a great threat to human health. This review summarizes the complex mechanisms underlying EBV latency programs and their roles in both viral persistence and disease development. We comprehensively analyze the four distinct latency programs (0, I, II, and III) and their associated gene expression patterns, with particular emphasis on the key viral proteins, the Epstein-Barr virus nuclear antigen EBNA1, EBNA2, EBNA3A/B/C, LMP1, and LMP2A/B. The review explores how these latency programs contribute to various EBV-associated malignancies and autoimmune conditions, including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and multiple sclerosis. We detail the multilayered regulation of EBV latency, encompassing epigenetic modifications, chromatin organization, and long-range genomic interactions. Recent advances in understanding the molecular mechanisms of EBV latency maintenance and the virus's interaction with host cellular machinery provide new insights into potential therapeutic approaches for EBV-associated diseases.
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http://dx.doi.org/10.1002/jmv.70501 | DOI Listing |
J Med Virol
September 2025
Cancer Virology Program, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are oncogenic human gammaherpesviruses (GHVs) associated with a broad spectrum of malignancies and chronic diseases. However, direct studies of these viruses in humans are limited by ethical constraints, technical challenges, and their strict species specificity. To overcome these barriers, researchers have developed surrogate models, with murine gammaherpesvirus 68 (MHV68) emerging as a tractable and widely utilized system.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Institute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. Electronic address:
Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) sustains viral latency and drives oncogenesis in EBV-driven malignancies such as nasopharyngeal carcinoma and lymphomas. The dimerization of EBNA1 acts as an indispensable molecular switch governing EBV latency and oncogenesis. Disruption of EBNA1 dimerization is a promising strategy, but existing small-molecule inhibitors lack sufficient specificity.
View Article and Find Full Text PDFCurr Top Microbiol Immunol
September 2025
School of Medicine, Bernal Institute, Limerick Digital Cancer Research Centre & Health Research Institute, University of Limerick, Limerick, Ireland.
Classical Hodgkin lymphoma (cHL) is a unique B cell malignancy characterised by the presence of Hodgkin/Reed-Sternberg (HRS) cells within an extensive inflammatory microenvironment. In approximately 40% of cases- particularly in the mixed cellularity subtype-HRS cells are infected with the Epstein-Barr virus (EBV). EBV-positive cHL displays a restricted pattern of viral gene expression (latency II), with functional contributions from EBNA1, LMP1, and LMP2A/B, as well as some non-coding RNAs.
View Article and Find Full Text PDFVaccines (Basel)
August 2025
Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China.
: It is still challenging to develop effective vaccines against tumorigenic human gammaherpesviruses such as Epstein-Barr virus (EBV). A major obstacle is the lack of a small animal model that reproduces the natural infection course of human gammaherpesviruses to allow for proper assessment of vaccine efficacy. Murine gammaherpesvirus 68 (MHV68) is a natural pathogen of wild rodents and laboratory mice and therefore can be used as a surrogate for human gammaherpesviruses to evaluate vaccination strategies.
View Article and Find Full Text PDFJ Transl Med
August 2025
Cancer Research Institute, Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, University of South China, Hunan, 421001, China.
Background: EBV-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer with EBV latency infection. EBV microRNAs, especially rightward transcript (BART) microRNAs, play key roles in the tumor growth of EBVaGC. However, the effects of EBV-miR-BART19-3p in EBVaGC remain largely unknown.
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