ArticlePLoS pathogens2019
Endocytosis of flavivirus NS1 is required for NS1-mediated endothelial hyperpermeability and is abolished by a single N-glycosylation site mutation.
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 57 papers.
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Who cites it
57 citing papers in PubMed, 89 citations in OpenAlex.
- Pericyte dysfunction alone may be insufficient to drive tick-borne orthoflavivirus non-structural protein 1-mediated microvascular permeability.The Journal of general virology · 2026Article
- Emerging viral infections: role of flavivirus NS1-mediated rewiring of PRR signaling.European cytokine network · 2026Review
- Host serum-circulating flavivirus NS1 co-opts mosquito miRNA processing to suppress early immune defense.Nature communications · 2026Article
- Dynamic structures of dengue virus serotype 2 secreted NS1 and their interactions with heparan sulfate.Nature communications · 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
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 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
- Glycans on non-structural protein 1 prevent premature T-cell mediated dengue virus clearance.EMBO molecular medicine · 2025Article
- Endothelial leak and knowledge gaps: yellow fever virus non-structural protein 1 and the antibodies that bind it.Virology journal · 2025Review
- Coatomer protein complex I is required for efficient secretion of dengue virus non-structural protein 1.Journal of virology · 2025Article
- Review
- Influenza A virus NS1 protein mimics oncogenic PI3K resulting in isoform specific cellular redistribution and activation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TBEV NS1 Induces Tissue-Specific Microvascular Endothelial Cell Permeability by Activating the TNF-α Signaling Pathway.International journal of molecular sciences · 2025Article
- Characterization of the Temporal Dynamics of the Endothelial-Mesenchymal-like Transition Induced by Soluble Factors from Dengue Virus Infection in Microvascular Endothelial Cells.International journal of molecular sciences · 2025Article
- Animal Models, Therapeutics, and Vaccine Approaches to Emerging and Re-Emerging Flaviviruses.Viruses · 2024Review
- Dengue virus NS1 leads to downregulation of HNF4 alpha in liver cells resulting in a decrease in coagulation factors I, V, X, and XIII, contributing to coagulopathy.Journal of virology · 2024Article
- Article
- The step-by-step assembly mechanism of secreted flavivirus NS1 tetramer and hexamer captured at atomic resolution.Science advances · 2024Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Arthropod-borne flaviviruses cause life-threatening diseases associated with endothelial hyperpermeability and vascular leak. We recently found that vascular leak can be triggered by dengue virus (DENV) non-structural protein 1 (NS1) via the disruption of the endothelial glycocalyx-like layer (EGL). However, the molecular determinants of NS1 required to trigger EGL disruption and the cellular pathway(s) involved remain unknown. Here we report that mutation of a single glycosylated residue of NS1 (N207Q) abolishes the ability of NS1 to trigger EGL disruption and induce endothelial hyperpermeability. Intriguingly, while this mutant bound to the surface of endothelial cells comparably to wild-type NS1, it was no longer internalized, suggesting that NS1 binding and internalization are distinct steps. Using endocytic pathway inhibitors and gene-specific siRNAs, we determined that NS1 was endocytosed into endothelial cells in a dynamin- and clathrin-dependent manner, which was required to trigger endothelial dysfunction in vitro and vascular leak in vivo. Finally, we found that the N207 glycosylation site is highly conserved among flaviviruses and is also essential for West Nile and Zika virus NS1 to trigger endothelial hyperpermeability via clathrin-mediated endocytosis. These data provide critical mechanistic insight into flavivirus NS1-induced pathogenesis, presenting novel therapeutic and vaccine targets for flaviviral diseases.
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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.