ArticleBlood advances2020
Inflammatory signaling in dengue-infected platelets requires translation and secretion of nonstructural protein 1.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 48 citations in OpenAlex.
- P2Y12-P-selectin-mediated platelet activation in a murine model of dengue-associated thrombocytopenia.EBioMedicine · 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
- 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
- Monocyte TLR2/4 as predictive biomarkers for progression from dengue warning signs to severe disease.Frontiers in immunology · 2026Article
- P-Selectin and Platelet-Monocyte Interaction in Inflammation: Mechanisms, Hypothesis, and Open Questions.Journal of inflammation research · 2026Review
- Flavivirus Nonstructural Protein 1‑Driven Coagulation via Tissue Factor-Bearing Microvesicles: A Pilot Study.ACS omega · 2025Article
- Review
- Dengue virus infection: how platelet-leukocyte crosstalk shapes thrombotic events and inflammation.Molecular biology reports · 2025Review
- Dengue infection changes the expressions of CD154 and CD148 in human platelets.Virus research · 2025Article
- Platelets in infection: intrinsic roles and functional outcomes.Frontiers in immunology · 2025Review
- Thrombocytopenia in dengue infection: mechanisms and a potential application.Expert reviews in molecular medicine · 2024Review
- The N and C-terminal deleted variant of the dengue virus NS1 protein is a potential candidate for dengue vaccine development.Scientific reports · 2024Article
- Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT)-Insights from Clinical Cases, In Vitro Studies and Murine Models.Journal of clinical medicine · 2023Review
- Dissecting Platelet's Role in Viral Infection: A Double-Edged Effector of the Immune System.International journal of molecular sciences · 2023Review
- Platelet derived exosomes disrupt endothelial cell monolayer integrity and enhance vascular inflammation in dengue patients.Frontiers in immunology · 2023Article
- Inflammasome activation by viral infection: mechanisms of activation and regulation.Frontiers in microbiology · 2023Review
- Review
- Platelet proteome reveals features of cell death, antiviral response and viral replication in covid-19.Cell death discovery · 2022Article
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging evidence identifies major contributions of platelets to inflammatory amplification in dengue, but the mechanisms of infection-driven platelet activation are not completely understood. Dengue virus nonstructural protein-1 (DENV NS1) is a viral protein secreted by infected cells with recognized roles in dengue pathogenesis, but it remains unknown whether NS1 contributes to the inflammatory phenotype of infected platelets. This study shows that recombinant DENV NS1 activated platelets toward an inflammatory phenotype that partially reproduced DENV infection. NS1 stimulation induced translocation of α-granules and release of stored factors, but not of newly synthesized interleukin-1β (IL-1β). Even though both NS1 and DENV were able to induce pro-IL-1β synthesis, only DENV infection triggered caspase-1 activation and IL-1β release by platelets. A more complete thromboinflammatory phenotype was achieved by synergistic activation of NS1 with classic platelet agonists, enhancing α-granule translocation and inducing thromboxane A2 synthesis (thrombin and platelet-activating factor), or activating caspase-1 for IL-1β processing and secretion (adenosine triphosphate). Also, platelet activation by NS1 partially depended on toll-like receptor-4 (TLR-4), but not TLR-2/6. Finally, the platelets sustained viral genome translation and replication, but did not support the release of viral progeny to the extracellular milieu, characterizing an abortive viral infection. Although DENV infection was not productive, translation of the DENV genome led to NS1 expression and release by platelets, contributing to the activation of infected platelets through an autocrine loop. These data reveal distinct, new mechanisms for platelet activation in dengue, involving DENV genome translation and NS1-induced platelet activation via platelet TLR4.
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