ArticlePLoS pathogens2019
Dengue virus nonstructural protein 1 activates platelets via Toll-like receptor 4, leading to thrombocytopenia and hemorrhage.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 182 citations in OpenAlex.
- Predictive markers for the early prognosis of dengue severity: A systematic review and meta-analysis.PLoS neglected tropical diseases · 2021Pooled it
- A replication-defective tick-borne encephalitis virus generated by NS1 trans-complementation confers robust protective efficacy.Virologica Sinica · 2026Article
- P2Y12-P-selectin-mediated platelet activation in a murine model of dengue-associated thrombocytopenia.EBioMedicine · 2026Article
- Beyond Platelet Destruction: A Mechanistic Understanding of Dengue Virus Non-Structural Proteins and Gene Regulatory Networks Driving Thrombocytopenia.Journal of thrombosis and thrombolysis · 2026Article
- Beyond Hemostasis: Platelet Biomarkers and Vascular-Immune Crosstalk in Dengue.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Tylvalosin tartrate inhibits PRRSV replication by suppressing cellular pyroptosis through the TLR4/NF-κB signaling pathway.Journal of virology · 2026Article
- Position Statement on the Management of Antithrombotic and Anticoagulant Therapy in Dengue - 2026.Arquivos brasileiros de cardiologia · 2026Article
- Dengue NS1 as a Driver of Immune-Mediated Pathogenesis.Tropical medicine and infectious disease · 2026Review
- Platelet-leucocyte interactions drive MMP-mediated tissue damage in tuberculosis.PLoS pathogens · 2026Article
- Secretory NS1' protein of orthoflavivirus promotes viral transmission to mosquitoes by suppressing the RNAi pathway.Science China. Life sciences · 2026Article
- Review
- Double-edged sword: flavivirus NS1 enhances human plasmin-mediated fibrinolysis while being targeted for cleavage and inactivation.The Journal of general virology · 2026Article
- Potential Mechanisms Underlying Bleeding During Infection With Hemorrhagic Fever Viruses.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Concurrent Scrub Typhus, Dengue, and Leptospirosis: A Rare Triple Co-Infection: A Case Report and Comprehensive Literature Review.Clinical case reports · 2026Article
- Monocyte TLR2/4 as predictive biomarkers for progression from dengue warning signs to severe disease.Frontiers in immunology · 2026Article
- Clinical characteristics of thrombocytopenia in tropical diseases and management in resource-limited settings.Research and practice in thrombosis and haemostasis · 2026Review
- Cellular Biology: Virus-Host Interactions and RNA Structure and Function.Current topics in microbiology and immunology · 2026Review
- Flavivirus NS1-triggered endothelial dysfunction promotes virus dissemination.PLoS pathogens · 2025Article
- Dengue Virus NS1 Binds Ephrin B1 to Trigger Endothelial Dysfunction.bioRxiv : the preprint server for biology · 2025Article
- Dengue virus NS1 protein does not activate TLR4 and has a modest effect on endothelial monolayer integrity compared to TNF.PLoS pathogens · 2025Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dengue virus (DENV) infection, the most common mosquito-transmitted viral infection, can cause a range of diseases from self-limiting dengue fever to life-threatening dengue hemorrhagic fever and shock syndrome. Thrombocytopenia is a major characteristic observed in both mild and severe dengue disease and is significantly correlated with the progression of dengue severity. Previous studies have shown that DENV nonstructural protein 1 (NS1), which can be secreted into patients' blood, can stimulate immune cells via Toll-like receptor 4 (TLR4) and can cause endothelial leakage. However, it is unclear whether DENV NS1 can directly induce platelet activation or cause thrombocytopenia during DENV infection. In this study, we first demonstrated that DENV but not Zika virus cell culture supernatant could induce P-selectin expression and phosphatidylserine (PS) exposure in human platelets, both of which were abolished when NS1 was depleted from the DENV supernatant. Similar results were found using recombinant NS1 from all four serotypes of DENV, and those effects were blocked in the presence of anti-NS1 F(ab')2, anti-TLR4 antibody, a TLR4 antagonist (Rhodobacter sphaeroides lipopolysaccharide, LPS-Rs) and a TLR4 signaling inhibitor (TAK242), but not polymyxin B (an LPS inhibitor). Moreover, the activation of platelets by DENV NS1 promoted subthreshold concentrations of adenosine diphosphate (ADP)-induced platelet aggregation and enhanced platelet adhesion to endothelial cells and phagocytosis by macrophages. Finally, we demonstrated that DENV-induced thrombocytopenia and hemorrhage were attenuated in TLR4 knockout and wild-type mice when NS1 was depleted from DENV supernatant. Taken together, these results suggest that the binding of DENV NS1 to TLR4 on platelets can trigger its activation, which may contribute to thrombocytopenia and hemorrhage during dengue infection.
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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.