ArticlePLoS pathogens2020
B cells infected with Type 2 Epstein-Barr virus (EBV) have increased NFATc1/NFATc2 activity and enhanced lytic gene expression in comparison to Type 1 EBV infection.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Integrating Flow Cytometry in the Diagnostic Work of HIV-Associated Hodgkin's Lymphomas.Journal of cellular and molecular medicine · 2026Review
- EBV Genome Variations and Association With Diseases.Journal of medical virology · 2026Review
- Relevance of Epstein-Barr Virus (EBV) miRNAs in EBV-Infected B Cells and B-Cell Lymphomas.Cancers · 2026Review
- EBV Type 1 versus Type 2: A determinant of NK cell anti-tumor activity in Burkitt lymphoma.bioRxiv : the preprint server for biology · 2026Article
- Clinical features and comorbidities of Epstein-Barr virus infection in childhood-onset systemic lupus erythematosus with a focus on macrophage activation syndrome: a cross-sectional study of 200 patients.Frontiers in immunology · 2026Article
- Epstein-Barr virus type 2 infection is associated with higher viral loads in pediatric tonsils from western Kenya.Microbiology spectrum · 2025Article
- Multiple sclerosis and infection: history, EBV, and the search for mechanism.Microbiology and molecular biology reviews : MMBR · 2025Review
- A Comparative Genomic Analysis of Epstein-Barr Virus Strains with a Focus on EBV2 Variability.International journal of molecular sciences · 2025Article
- The NFATC2/Nrf2 cascade regulates spinal cord ischemia-reperfusion injury by controlling inflammation, apoptosis and oxidative stress.Regenerative therapy · 2025Article
- Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome.BMC genomics · 2024Article
- The viral etiology of EBV-associated gastric cancers contributes to their unique pathology, clinical outcomes, treatment responses and immune landscape.Frontiers in immunology · 2024Review
- Effective Pruning for Top-k Feature Search on the Basis of SHAP Values.IEEE access : practical innovations, open solutions · 2024Article
- Mendelian randomisation identifies priority groups for prophylactic EBV vaccination.BMC infectious diseases · 2023Article
- A comprehensive single cell data analysis of lymphoblastoid cells reveals the role of super-enhancers in maintaining EBV latency.Journal of medical virology · 2023Article
- Regulation of B cell receptor signalling by Epstein-Barr virus nuclear antigens.The Biochemical journal · 2022Article
- Epstein-Barr Virus (EBV) Epithelial Associated Malignancies: Exploring Pathologies and Current Treatments.International journal of molecular sciences · 2022Review
- Type 1 and Type 2 Epstein-Barr viruses induce proliferation, and inhibit differentiation, in infected telomerase-immortalized normal oral keratinocytes.PLoS pathogens · 2022Article
- EBV genome variations enhance clinicopathological features of nasopharyngeal carcinoma in a non-endemic region.Cancer science · 2022Article
- Epstein-Barr Virus (EBV) Is Mostly Latent and Clonal in Angioimmunoblastic T Cell Lymphoma (AITL).Cancers · 2022Article
- Reduced IRF4 expression promotes lytic phenotype in Type 2 EBV-infected B cells.PLoS pathogens · 2022Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Humans are infected with two distinct strains (Type 1 (T1) and Type 2 (T2)) of Epstein-Barr virus (EBV) that differ substantially in their EBNA2 and EBNA 3A/B/C latency genes and the ability to transform B cells in vitro. While most T1 EBV strains contain the "prototype" form of the BZLF1 immediate-early promoter ("Zp-P"), all T2 strains contain the "Zp-V3" variant, which contains an NFAT binding motif and is activated much more strongly by B-cell receptor signalling. Whether B cells infected with T2 EBV are more lytic than cells infected with T1 EBV is unknown. Here we show that B cells infected with T2 EBV strains (AG876 and BL5) have much more lytic protein expression compared to B cells infected with T1 EBV strains (M81, Akata, and Mutu) in both a cord blood-humanized (CBH) mouse model and EBV-transformed lymphoblastoid cell lines (LCLs). Although T2 LCLs grow more slowly than T1 LCLs, both EBV types induce B-cell lymphomas in CBH mice. T1 EBV strains (M81 and Akata) containing Zp-V3 are less lytic than T2 EBV strains, suggesting that Zp-V3 is not sufficient to confer a lytic phenotype. Instead, we find that T2 LCLs express much higher levels of activated NFATc1 and NFATc2, and that cyclosporine (an NFAT inhibitor) and knockdown of NFATc2 attenuate constitutive lytic infection in T2 LCLs. Both NFATc1 and NFATc2 induce lytic EBV gene expression when combined with activated CAMKIV (which is activated by calcium signaling and activates MEF2D) in Burkitt Akata cells. Together, these results suggest that B cells infected with T2 EBV are more lytic due to increased activity of the cellular NFATc1/c2 transcription factors in addition to the universal presence of the Zp-V3 form of BZLF1 promoter.
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