ArticlePLoS pathogens2017
The Epstein-Barr virus miR-BHRF1-1 targets RNF4 during productive infection to promote the accumulation of SUMO conjugates and the release of infectious virus.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- The role of Epstein-Barr virus in NK/T cell lymphoproliferative disorders: molecular mechanisms and potential therapeutic strategies.Frontiers in immunology · 2026Review
- Implications of EBV-Encoded and EBV-Related miRNAs in Tumors.Current gene therapy · 2025Review
- Changes in SUMO-modified proteins in Epstein-Barr virus infection identifies reciprocal regulation of TRIM24/28/33 complexes and the lytic switch BZLF1.PLoS pathogens · 2023Article
- Human immunodeficiency virus type 1 impairs sumoylation.Life science alliance · 2022Article
- Landscape of EBV-positive gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Review
- The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the activity of topoisomerase II during productive infection.PLoS pathogens · 2021Article
- Bioinformatics analysis of miRNA and mRNA expression profiles to reveal the key miRNAs and genes in osteoarthritis.Journal of orthopaedic surgery and research · 2021Article
- Immune Escape by Non-coding RNAs of the Epstein Barr Virus.Frontiers in microbiology · 2021Review
- Epstein-Barr Virus: How Its Lytic Phase Contributes to Oncogenesis.Microorganisms · 2020Review
- Latency and lytic replication in Epstein-Barr virus-associated oncogenesis.Nature reviews. Microbiology · 2019Review
- Article
- Epstein-Barr virus microRNAs regulate B cell receptor signal transduction and lytic reactivation.PLoS pathogens · 2019Article
- Using glycyrrhizic acid to target sumoylation processes during Epstein-Barr virus latency.PloS one · 2019Article
- A genome-wide screen of Epstein-Barr virus proteins that modulate host SUMOylation identifies a SUMO E3 ligase conserved in herpesviruses.PLoS pathogens · 2018Article
- Lactic Acid Downregulates Viral MicroRNA To Promote Epstein-Barr Virus-Immortalized B Lymphoblastic Cell Adhesion and Growth.Journal of virology · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Post-translational modification by the Small Ubiquitin-like Modifier (SUMO) regulates a variety of cellular functions, and is hijacked by viruses to remodel the host cell during latent and productive infection. Here we have monitored the activity of the SUMO conjugation machinery in cells productively infected with Epstein-Barr virus (EBV). We found that SUMO2/3 conjugates accumulate during the late phase of the productive virus cycle, and identified several viral proteins as bone fide SUMOylation substrates. Analysis of the mechanism involved in the accumulation of SUMOylated proteins revealed upregulation of several components of the SUMO-conjugation machinery and post-transcriptional downregulation of the SUMO-targeted ubiquitin ligase RNF4. The latter effect was mediated by selective inhibition of RNF4 protein expression by the viral miR-BHRF1-1. Reconstitution of RNF4 in cells expressing an inducible miR-BHRF1-1 sponge or a miR-BHRF1-1 resistant RNF4 was associated with reduced levels of early and late viral proteins and impaired virus release. These findings illustrate a novel strategy for viral interference with the SUMO pathway, and identify the EBV miR-BHRF1-1 and the cellular RNF4 as regulators of the productive virus cycle.
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