# Epstein–Barr virus-associated lymphoma: current understanding and treatment strategies

**Authors:** Hee Young Ju

PMC · DOI: 10.1007/s44313-026-00127-4 · Blood Research · 2026-03-07

## TL;DR

This review discusses how Epstein–Barr virus causes lymphomas and explores current and emerging treatment strategies for these cancers.

## Contribution

The paper provides a comprehensive review of EBV's role in lymphoma pathogenesis and evaluates current therapeutic approaches.

## Key findings

- EBV establishes latent infections in B cells, contributing to lymphoma development through various mechanisms.
- EBV-positive lymphomas are generally associated with worse clinical outcomes compared to EBV-negative cases.
- The review highlights therapeutic strategies targeting EBV-related pathways and immune evasion mechanisms.

## Abstract

Epstein–Barr virus (EBV) infection is well-known for its high prevalence rate, association with several diseases including cancer and autoimmune conditions, and a wide variety of symptoms and prognosis. When acquired at a young age, primary infections are often asymptomatic; however, in adolescence and young adulthood, symptomatic infections develop, such as in infectious mononucleosis. A special feature of EBV infection is its ability to establish a latent infection in B cells which can lead to long-term infection. Subsequent cellular transformation and viral protein expression can result to EBV-mediated carcinogenesis. Latent proteins expressed by EBV play a role in the pathogenesis of EBV infection and carcinogenesis. These proteins are responsible for a diverse range of functions including cell transformation, cell reprogramming, immune evasion, immune suppression, angiogenesis, cell cycle regulation, and B-cell receptor mimicry.

EBV infection is associated with diffuse large B-cell lymphoma, Hodgkin lymphoma, NK/T cell lymphoma, Burkitt lymphoma, post-transplant lymphoproliferative disorders, and primary CNS lymphoma. The clinical presentation varies depending on the specific disease and EBV status, with EBV-positive lymphomas generally associated with poorer prognosis than EBV-negative cases.

This review aimed to examine the current understanding of the pathogenesis of EBV-associated lymphoma and to evaluate emerging and accepted therapeutic strategies.

## Linked entities

- **Diseases:** diffuse large B-cell lymphoma (MONDO:0018905), Hodgkin lymphoma (MONDO:0004952), NK/T cell lymphoma (MONDO:0019472), Burkitt lymphoma (MONDO:0007243), primary CNS lymphoma (MONDO:0002571)

## Full-text entities

- **Genes:** EBNA-LP [NCBI Gene 17494199], ADRA2B (adrenoceptor alpha 2B) [NCBI Gene 151] {aka ADRA2L1, ADRA2RL1, ADRARL1, ALPHA2BAR, FAME2, alpha-2BAR}, MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}, CD40 (CD40 molecule) [NCBI Gene 958] {aka Bp50, CDW40, TNFRSF5, p50}, IRF3 (interferon regulatory factor 3) [NCBI Gene 3661] {aka IIAE7}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, EBNA [NCBI Gene 17494235], MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, PDCD1LG2 (programmed cell death 1 ligand 2) [NCBI Gene 80380] {aka B7DC, Btdc, CD273, PD-L2, PDCD1L2, PDL2}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, PDLIM7 (PDZ and LIM domain 7) [NCBI Gene 9260] {aka LMP1, LMP3}, S1PR2 (sphingosine-1-phosphate receptor 2) [NCBI Gene 9294] {aka AGR16, DFNB68, EDG-5, EDG5, Gpcr13, H218}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, PPARGC1B (PPARG coactivator 1 beta) [NCBI Gene 133522] {aka ERRL1, PERC, PGC-1(beta), PGC1B}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, SYK (spleen associated tyrosine kinase) [NCBI Gene 6850] {aka IMD82, p72-Syk}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, AICDA (activation induced cytidine deaminase) [NCBI Gene 57379] {aka AID, ARP2, CDA2, HEL-S-284, HIGM2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, PSMB9 (proteasome 20S subunit beta 9) [NCBI Gene 5698] {aka LMP2, PRAAS3, PRAAS6, PSMB6i, RING12, beta1i}, CDA (cytidine deaminase) [NCBI Gene 978] {aka CDD}, TCF3 (transcription factor 3) [NCBI Gene 6929] {aka AGM8, AGM8A, AGM8B, E2A, E47, ITF1}, ID3 (inhibitor of DNA binding 3) [NCBI Gene 3399] {aka HEIR-1, bHLHb25}, BCR (BCR activator of RhoGEF and GTPase) [NCBI Gene 613] {aka ALL, BCR1, CML, D22S11, D22S662, PHL}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** toxicity (MESH:D064420), infected (MESH:D007239), viral infections (MESH:D014777), HRS (MESH:C535516), immunodeficiency (MESH:D007153), NK/T cell lymphoma (MESH:D016399), P. falciparum co-infection (MESH:D060085), nasopharyngeal carcinoma (MESH:D000077274), primary effusion lymphomas (MESH:D054685), human immunodeficiency virus infection (MESH:D015658), DLBCL (MESH:D016403), EBV-associated lymphoproliferative disorders (MESH:D008232), inborn errors (MESH:D008661), Lymphoid Neoplasms (MESH:D008223), Plasmodium falciparum malaria (MESH:D016778), Haematolymphoid Tumors (MESH:D009369), mitochondrial dysfunction (MESH:D028361), EBV infections (MESH:D020031), extranodal natural killer/T cell lymphoma (MESH:D000077428), Kaposi sarcoma-associated herpes virus-associated (MESH:D012514), latent B cell (MESH:D015448), carcinogenesis (MESH:D063646), extranodal NK/T cell lymphoma (MESH:D054391), Burkitt lymphoma (MESH:D002051), Classical Hodgkin lymphoma (MESH:D006689), gastric carcinoma (MESH:D013274), autoimmune conditions (MESH:D001327), infectious mononucleosis (MESH:D007244)
- **Chemicals:** nanatinostat (MESH:C555225), pembrolizumab (MESH:C582435), valganciclovir (MESH:D000077562), baltaleucel T (-), reactive oxygen species (MESH:D017382), flavonoid (MESH:D005419), arginine butyrate (MESH:C033018), hydroxamic acid (MESH:D006877), CBL0137 (MESH:C000600493), Quercetin (MESH:D011794), ganciclovir (MESH:D015774), decitabine (MESH:D000077209)
- **Species:** Homo sapiens (human, species) [taxon 9606], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376]

## Full text

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## Figures

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## References

6 references — full list in the complete paper: https://tomesphere.com/paper/PMC12972171/full.md

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Source: https://tomesphere.com/paper/PMC12972171