ArticlePloS one2016
Acute Systemic Infection with Dengue Virus Leads to Vascular Leakage and Death through Tumor Necrosis Factor-α and Tie2/Angiopoietin Signaling in Mice Lacking Type I and II Interferon Receptors.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Divergent effects of tumor necrosis factor (TNF) in sepsis: a meta-analysis of experimental studies.Critical care (London, England) · 2024Pooled it
- Systematic review of the role of angiopoietin-1 and angiopoietin-2 in Plasmodium species infections: biomarkers or therapeutic targets?Malaria journal · 2016Pooled it
- Dengue virus NS1 protein does not activate TLR4 and has a modest effect on endothelial monolayer integrity compared to TNF.PLoS pathogens · 2025Article
- Cytokine storm and vascular leakage in severe dengue: insights from single-cell RNA profiling.Life science alliance · 2025Article
- The Angiopoietin-Tie-2 Axis in Children and Young Adults with Dengue Virus Infection in the Philippines.The American journal of tropical medicine and hygiene · 2024Article
- Altered neutrophil responses to dengue virus serotype three: delayed apoptosis is regulated by stabilisation of Mcl-1.Scientific reports · 2024Article
- N-glycosylation of viral glycoprotein is a novel determinant for the tropism and virulence of highly pathogenic tick-borne bunyaviruses.PLoS pathogens · 2024Article
- Genetic regions affecting the replication and pathogenicity of dengue virus type 2.PLoS neglected tropical diseases · 2024Article
- Gut microbiota depletion and FXR inhibition exacerbates zonal hepatotoxicity of sunitinib.Theranostics · 2024Article
- Exploring adjunctive therapies for cerebral malaria.Frontiers in cellular and infection microbiology · 2024Review
- Mice, myeloid cells, and dengue: a new model for unraveling vascular leakage mysteries.Frontiers in microbiology · 2024Article
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Dengue virus infection induces selective expansion of Vγ4 and Vγ6TCR γδ T cells in the small intestine and a cytokine storm driving vascular leakage in mice.PLoS neglected tropical diseases · 2023Article
- Development of a novel virus-like particle-based vaccine for preventing tick-borne encephalitis virus infection.Virologica Sinica · 2023Article
- Experimental Yellow Fever in Squirrel Monkey: Characterization of Liver In Situ Immune Response.Viruses · 2023Article
- Neutralizing mAbs against SFTS Virus Gn Protein Show Strong Therapeutic Effects in an SFTS Animal Model.Viruses · 2022Article
- Angiopoietin-1 protects against endotoxin-induced neonatal lung injury and alveolar simplification in mice.Pediatric research · 2022Article
- MDA5 signaling induces type 1 IFN- and IL-1-dependent lung vascular permeability which protects mice from opportunistic fungal infection.Frontiers in immunology · 2022Article
- SARS-CoV-2 in Urine May Predict a Severe Evolution of COVID-19.Journal of clinical medicine · 2021Article
- Specific Interaction of DDX6 with an RNA Hairpin in the 3' UTR of the Dengue Virus Genome Mediates GJournal of virology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe dengue is caused by host responses to viral infection, but the pathogenesis remains unknown. This is, in part, due to the lack of suitable animal models. Here, we report a non-mouse-adapted low-passage DENV-3 clinical isolate, DV3P12/08, derived from recently infected patients. DV3P12/08 caused a lethal systemic infection in type I and II IFN receptor KO mice (IFN-α/β/γR KO mice), which have the C57/BL6 background. Infection with DV3P12/08 induced a cytokine storm, resulting in severe vascular leakage (mainly in the liver, kidney and intestine) and organ damage, leading to extensive hemorrhage and rapid death. DV3P12/08 infection triggered the release of large amounts of TNF-α, IL-6, and MCP-1. Treatment with a neutralizing anti-TNF-α antibody (Ab) extended survival and reduced liver damage without affecting virus production. Anti-IL-6 neutralizing Ab partly prolonged mouse survival. The anti-TNF-α Ab suppressed IL-6, MCP-1, and IFN-γ levels, suggesting that the severe response to infection was triggered by TNF-α. High levels of TNF-α mRNA were expressed in the liver and kidneys, but not in the small intestine, of infected mice. Conversely, high levels of IL-6 mRNA were expressed in the intestine. Importantly, treatment with Angiopoietin-1, which is known to stabilize blood vessels, prolonged the survival of DV3P12/08-infected mice. Taken together, the results suggest that an increased level of TNF-α together with concomitant upregulation of Tie2/Angiopoietin signaling have critical roles in severe dengue infection.
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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.