# Epstein‐Barr Virus Infection at Single‐Cell Resolution

**Authors:** Elliott D. SoRelle

PMC · DOI: 10.1002/jmv.70825 · Journal of Medical Virology · 2026-02-05

## TL;DR

This paper reviews how single-cell techniques have advanced our understanding of Epstein-Barr virus infection and its impact on diseases.

## Contribution

The paper provides a comprehensive overview of recent advancements and open questions in EBV single-cell and spatial-omics research.

## Key findings

- Single-cell assays are shifting from characterization to functional studies of EBV-host interactions.
- Spatial-omics and single-cell sequencing workflows are being used to uncover clinically relevant insights.
- Open questions in EBV pathogenesis remain, which could be addressed with future single-cell techniques.

## Abstract

Epstein‐Barr virus (EBV) infection has been studied at single‐cell resolution for six decades and counting. Such investigations can reveal virus‐host interactions and their dependence on viral strain, cellular niche, infection program, immune response regulation, and time. Understanding these factors is paramount to treating EBV‐associated cancers and autoimmune diseases. This review examines the state of the field in EBV single‐cell and spatial‐omics spanning experimental models and clinical samples. Topics of primary interest include the growing adoption and emerging biological themes from single‐cell assays and analyses, the shift from characterization toward functional single‐cell studies, and strategies to maximize clinically relevant insights from dense single‐cell and spatial datasets. Ancillary topics include the historical evolution of the single‐cell EBV field and end‐to‐end single‐cell sequencing workflows. Special attention is given to open questions in molecular mechanisms of EBV pathogenesis and how they might be resolved by future studies utilizing single‐cell techniques.

## Full-text entities

- **Genes:** TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, Tbx21 (T-box 21) [NCBI Gene 57765] {aka TBT1, Tbet, Tblym}, LAG3 (lymphocyte activating 3) [NCBI Gene 3902] {aka CD223}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, TBX21 (T-box transcription factor 21) [NCBI Gene 30009] {aka IMD88, T-PET, T-bet, TBET, TBLYM}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, CD27 (CD27 molecule) [NCBI Gene 939] {aka S152, S152. LPFS2, T14, TNFRSF7, Tp55}, HAVCR2 (hepatitis A virus cellular receptor 2) [NCBI Gene 84868] {aka CD366, HAVcr-2, KIM-3, SPTCL, TIM3, TIMD-3}, TIGIT (T cell immunoreceptor with Ig and ITIM domains) [NCBI Gene 201633] {aka VSIG9, VSTM3, WUCAM}, ISG15 (ISG15 ubiquitin like modifier) [NCBI Gene 9636] {aka G1P2, IFI15, IMD38, IP17, UCRP, hUCRP}, SP140L (SP140 like nuclear body protein) [NCBI Gene 93349], HEPACAM (hepatic and glial cell adhesion molecule) [NCBI Gene 220296] {aka GlialCAM, MLC2A, MLC2B}, IRF4 (interferon regulatory factor 4) [NCBI Gene 3662] {aka IMD131, LSIRF, MUM1, NF-EM5, SHEP8}, BCR (BCR activator of RhoGEF and GTPase) [NCBI Gene 613] {aka ALL, BCR1, CML, D22S11, D22S662, PHL}, GRN (granulin precursor) [NCBI Gene 2896] {aka CLN11, FTD2, GEP, GP88, PCDGF, PEPI}, SP100 (SP100 nuclear body protein) [NCBI Gene 6672] {aka lysp100b}, EPHA2 (EPH receptor A2) [NCBI Gene 1969] {aka ARCC2, CTPA, CTPP1, CTRCT6, ECK}, Bcl6 (B cell leukemia/lymphoma 6) [NCBI Gene 12053] {aka Bcl5}, NTRK2 (neurotrophic receptor tyrosine kinase 2) [NCBI Gene 4915] {aka DEE58, EIEE58, GP145-TrkB, OBHD, TRKB, trk-B}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, IRF7 (interferon regulatory factor 7) [NCBI Gene 3665] {aka IMD39, IRF-7, IRF-7H, IRF7A, IRF7B, IRF7C}, ALDH1A1 (aldehyde dehydrogenase 1 family member A1) [NCBI Gene 216] {aka ALDC, ALDH-E1, ALDH1, ALDH11, HEL-9, HEL-S-53e}, IRF3 (interferon regulatory factor 3) [NCBI Gene 3661] {aka IIAE7}, FCGR3A (Fc gamma receptor IIIa) [NCBI Gene 2214] {aka CD16-II, CD16A, FCG3, FCGR3, FCRIIIA, FcGRIIIA}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, CCR6 (C-C motif chemokine receptor 6) [NCBI Gene 1235] {aka BN-1, C-C CKR-6, CC-CKR-6, CCR-6, CD196, CKR-L3}, LY6K (lymphocyte antigen 6 family member K) [NCBI Gene 54742] {aka CT97, HSJ001348, URLC10, ly-6K}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, Fcr (Fc receptor) [NCBI Gene 109615], Cxcr3 (C-X-C motif chemokine receptor 3) [NCBI Gene 12766] {aka Cd183, Cmkar3}, PDLIM7 (PDZ and LIM domain 7) [NCBI Gene 9260] {aka LMP1, LMP3}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, IRF1 (interferon regulatory factor 1) [NCBI Gene 3659] {aka IMD117, IRF-1, MAR}, FCER1G (Fc epsilon receptor Ig) [NCBI Gene 2207] {aka FCRG}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CCL3 (C-C motif chemokine ligand 3) [NCBI Gene 6348] {aka G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI}, CXCR3 (C-X-C motif chemokine receptor 3) [NCBI Gene 2833] {aka CD182, CD183, CKR-L2, CMKAR3, GPR9, IP10-R}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, IRF8 (interferon regulatory factor 8) [NCBI Gene 3394] {aka H-ICSBP, ICSBP, ICSBP1, IMD32A, IMD32B, IRF-8}, F2R (coagulation factor II thrombin receptor) [NCBI Gene 2149] {aka CF2R, HTR, PAR-1, PAR1, TR}, IRF9 (interferon regulatory factor 9) [NCBI Gene 10379] {aka IRF-9, ISGF3, ISGF3G, p48}
- **Diseases:** RA (MESH:D001172), epithelial carcinomas (MESH:D009375), Angioimmunoblastic T cell lymphoma (MESH:D016399), HLH (MESH:D051359), Cancer (MESH:D009369), GA (MESH:D013274), SLE (MESH:D008180), cytotoxicity (MESH:D064420), IM (MESH:D007244), Lymphoid Malignancies (MESH:D008223), PSC (MESH:D015209), PLWH (MESH:C000719191), Lymphoproliferative (MESH:D008232), chronic infection (MESH:D000088562), Autoimmune and Inflammatory Diseases (MESH:D001327), infected (MESH:D007239), DLBCL (MESH:D016403), MS (MESH:D009103), PC (MESH:D015324), NPC (MESH:D000077274), GC (MESH:C548085), SARS-CoV-2 sequelae (MESH:D000094024), Epithelial Malignancies (MESH:D002277), BL (MESH:D002051), pSS (MESH:D012859), inflammation (MESH:D007249), MIS-C (MESH:C000705967), CAEBV (MESH:D020031), type 1 diabetes (MESH:D003922), HIV-NHL (MESH:D008228), viral diseases (MESH:D014777), HL (MESH:C538324), SARS-CoV-2 infection (MESH:D000086382), Hodgkin lymphoma (MESH:D006689), Hodgkin Reed-Sternberg (MESH:C535516), autoinflammatory liver disease (MESH:D008107), B cell malignancies (MESH:D016393)
- **Chemicals:** l-kynurenine (MESH:D007737), phorbol ester (MESH:D010703)
- **Species:** human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Saimiriine gammaherpesvirus 2 (Herpesvirus saimiri, no rank) [taxon 10381], Human immunodeficiency virus 1 (no rank) [taxon 11676], Homo sapiens (human, species) [taxon 9606], Human betaherpesvirus 6 (species) [taxon 10368], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** BL5 — Homo sapiens (Human), Burkitt lymphoma, Cancer cell line (CVCL_M563), B95-8 — Saguinus oedipus (Cotton-top tamarin), Transformed cell line (CVCL_1953), NPC43 — Homo sapiens (Human), Nasopharyngeal carcinoma, Cancer cell line (CVCL_UH64)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12875166/full.md

## References

89 references — full list in the complete paper: https://tomesphere.com/paper/PMC12875166/full.md

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Source: https://tomesphere.com/paper/PMC12875166