ArticlePLoS pathogens2018
A cancer-associated Epstein-Barr virus BZLF1 promoter variant enhances lytic infection.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
72 citing papers in PubMed, 90 citations in OpenAlex.
- Natural Variations in BRLF1 Promoter Contribute to the Elevated Reactivation Level of Epstein-Barr Virus in Endemic Areas of Nasopharyngeal Carcinoma.EBioMedicine · 2018Trial
- Modulation of DNA Damage by Epstein-Barr Virus (EBV).Viruses · 2026Review
- EBV Genome Variations and Association With Diseases.Journal of medical virology · 2026Review
- Article
- Burkitt Lymphoma-A Guide to Biological Features, Diagnosis and Differential Diagnosis.Cancers · 2026Review
- Epstein-Barr virus pathogenesis and emerging control strategies.Nature reviews. Microbiology · 2025Review
- Epstein-Barr virus type 2 infection is associated with higher viral loads in pediatric tonsils from western Kenya.Microbiology spectrum · 2025Article
- Gammaherpesvirus infection unveils exaggerated germinal center responses in an SR-BI-deficient host.Journal of virology · 2025Article
- Apolipoprotein E selectively supports gammaherpesvirus replication in macrophages.Journal of virology · 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
- Article
- Curcumin derivative C210 induces Epstein-Barr virus lytic cycle and inhibits virion production by disrupting Hsp90 function.Scientific reports · 2024Article
- Epstein-Barr virus as a potentiator of autoimmune diseases.Nature reviews. Rheumatology · 2024Review
- Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.PLoS pathogens · 2024Article
- Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.bioRxiv : the preprint server for biology · 2024Article
- Lytic and Latent Genetic Diversity of the Epstein-Barr Virus Reveals Raji-Related Variants from Southeastern Brazil Associated with Recombination Markers.International journal of molecular sciences · 2024Article
- Establishment and Characterization of an Epstein-Barr Virus-positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma.Cancer research communications · 2024Article
- Review
- Host genetic variants, Epstein-Barr virus subtypes, and the risk of nasopharyngeal carcinoma: Assessment of interaction and mediation.Cell genomics · 2024Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Latent Epstein-Barr virus (EBV) infection contributes to both B-cell and epithelial-cell malignancies. However, whether lytic EBV infection also contributes to tumors is unclear, although the association between malaria infection and Burkitt lymphomas (BLs) may involve excessive lytic EBV replication. A particular variant of the viral promoter (Zp) that controls lytic EBV reactivation is over-represented, relative to its frequency in non-malignant tissue, in EBV-positive nasopharyngeal carcinomas and AIDS-related lymphomas. To date, no functional differences between the prototype Zp (Zp-P) and the cancer-associated variant (Zp-V3) have been identified. Here we show that a single nucleotide difference between the Zp-V3 and Zp-P promoters creates a binding site for the cellular transcription factor, NFATc1, in the Zp-V3 (but not Zp-P) variant, and greatly enhances Zp activity and lytic viral reactivation in response to NFATc1-inducing stimuli such as B-cell receptor activation and ionomycin. Furthermore, we demonstrate that restoring this NFATc1-motif to the Zp-P variant in the context of the intact EBV B95.8 strain genome greatly enhances lytic viral reactivation in response to the NFATc1-activating agent, ionomycin, and this effect is blocked by the NFAT inhibitory agent, cyclosporine, as well as NFATc1 siRNA. We also show that the Zp-V3 variant is over-represented in EBV-positive BLs and gastric cancers, and in EBV-transformed B-cell lines derived from EBV-infected breast milk of Kenyan mothers that had malaria during pregnancy. These results demonstrate that the Zp-V3 enhances EBV lytic reactivation to physiologically-relevant stimuli, and suggest that increased lytic infection may contribute to the increased prevalence of this variant in EBV-associated malignancies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.