ArticleiScience2023
Differential localization of dengue virus protease affects cell homeostasis and triggers to thrombocytopenia.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- XPO1-dependent nuclear export regulates NS3 localization and promotes DENV-2 replication through mitochondrial remodeling and interferon suppression.Nucleus (Austin, Tex.) · 2026Article
- Beyond the Capsid: How Can Post-Translational Modifications Modulate the Multifunctionality of the Orthoflavivirus Capsid Protein?Molecules (Basel, Switzerland) · 2026Review
- The Flavivirus NS3 Protein: Its Multifaceted Roles and Therapeutic Potential.Journal of medical virology · 2026Review
- Host protein cleavage by Dengue and Zika virus NS3 proteases: from substrate identification to potential biological consequences.Frontiers in cellular and infection microbiology · 2026Review
- The Impacts of Dengue Virus Infection on Mitochondrial Functions and Dynamics.International journal of molecular sciences · 2025Review
- Aberrant systemic acute-phase complement responses in conjunction with soluble CR1 attribute to varying grades of dengue disease severity.Frontiers in immunology · 2025Article
- Thrombocytopenia in dengue infection: mechanisms and a potential application.Expert reviews in molecular medicine · 2024Review
- Dengue virus non-structural protein 3 inhibits mitochondrial respiration by impairing complex I function.mSphere · 2024Article
- Analysis of Cleavage Activity of Dengue Virus Protease by Co-transfections.Bio-protocol · 2024Article
- Computational Advancement towards the Identification of Natural Inhibitors for Dengue Virus: A Brief Review.Combinatorial chemistry & high throughput screening · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombocytopenia is one of the symptoms of many virus infections which is the "hallmark" in the case of dengue virus. In this study, we show the differential localization of existing two forms of dengue virus protease, i.e., NS2BNS3 to the nucleus and NS3 to the nucleus and mitochondria. We also report a nuclear transcription factor, erythroid differentiation regulatory factor 1 (EDRF1), as the substrate for this protease. EDRF1 regulates the expression and activity of GATA1, which in turn controls spectrin synthesis. Both GATA1 and spectrins are required for platelet formation. On the other hand, we found that the mitochondrial activities will be damaged by NS3 localization which cleaves GrpEL1, a co-chaperone of mitochondrial Hsp70. Levels of both EDRF1 and GrpEL1 were found to deteriorate in dengue virus-infected clinical samples. Hence, we conclude that NS2BNS3-mediated EDRF1 cleavage and the NS3-led mitochondrial dysfunction account for thrombocytopenia.
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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.