ArticlePLoS pathogens2014
Shed GP of Ebola virus triggers immune activation and increased vascular permeability.
Article in PLoS pathogens, 2014. 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.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- A systematic review of the immuno-inflammatory dysfunction secondary to viral hemorrhagic fevers; Ebola and Lassa fever.PLoS neglected tropical diseases · 2025Pooled it
- Ebola virus glycoprotein stimulates IL-18-dependent natural killer cell responses.The Journal of clinical investigation · 2020Trial
- Marburg Virus Glycoprotein Is a Remarkable Virulent Factor Linked to Hemorrhagic Pathology: Evidence from Multimodal Experimental Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- In Silico Modeling of Structural Compatibility and Alignment Between Viral Class I Fusion Cores and Human TLR4/MD-2.International journal of molecular sciences · 2026Article
- Review
- Nanobody targeting glycan cap confers broad orthoebolavirus neutralization.Virologica Sinica · 2026Article
- Article
- Ebola virus disease: A persistent challenge in global health security.Open veterinary journal · 2026Review
- Potential Mechanisms Underlying Bleeding During Infection With Hemorrhagic Fever Viruses.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Ebola virus matrix protein VP40 triggers inflammatory responses linked to the ebolavirus virulence.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Computational Design of Broad-Spectrum Ebola Antibodies through Framework and Complementarity-Determining Region Synergistic Optimization.Research (Washington, D.C.) · 2026Article
- Roles of endothelial cells during infection.Current opinion in immunology · 2025Review
- Article
- Ebola virus' hidden target: virus transmission to and infection of skin.Journal of virology · 2025Article
- Antibodies targeting Crimean-Congo hemorrhagic fever virus GP38 limit vascular leak and viral spread.Science translational medicine · 2025Article
- The implication of dendritic cells in lung diseases: Immunological role of toll-like receptor 4.Genes & diseases · 2024Review
- Ebola virus shed glycoprotein is toxic to human T, B, and natural killer lymphocytes.iScience · 2023Article
- Ebola virus-like particles reprogram cellular metabolism.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Antibodies against the Ebola virus soluble glycoprotein are associated with long-term vaccine-mediated protection of non-human primates.Cell reports · 2023Article
- Role of Siglecs in viral infections: A double-edged sword interaction.Molecular aspects of medicine · 2023Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During Ebola virus (EBOV) infection a significant amount of surface glycoprotein GP is shed from infected cells in a soluble form due to cleavage by cellular metalloprotease TACE. Shed GP and non-structural secreted glycoprotein sGP, both expressed from the same GP gene, have been detected in the blood of human patients and experimentally infected animals. In this study we demonstrate that shed GP could play a particular role during EBOV infection. In effect it binds and activates non-infected dendritic cells and macrophages inducing the secretion of pro- and anti-inflammatory cytokines (TNFα, IL1β, IL6, IL8, IL12p40, and IL1-RA, IL10). Activation of these cells by shed GP correlates with the increase in surface expression of co-stimulatory molecules CD40, CD80, CD83 and CD86. Contrary to shed GP, secreted sGP activates neither DC nor macrophages while it could bind DCs. In this study, we show that shed GP activity is likely mediated through cellular toll-like receptor 4 (TLR4) and is dependent on GP glycosylation. Treatment of cells with anti-TLR4 antibody completely abolishes shed GP-induced activation of cells. We also demonstrate that shed GP activity is negated upon addition of mannose-binding sera lectin MBL, a molecule known to interact with sugar arrays present on the surface of different microorganisms. Furthermore, we highlight the ability of shed GP to affect endothelial cell function both directly and indirectly, demonstrating the interplay between shed GP, systemic cytokine release and increased vascular permeability. In conclusion, shed GP released from virus-infected cells could activate non-infected DCs and macrophages causing the massive release of pro- and anti-inflammatory cytokines and effect vascular permeability. These activities could be at the heart of the excessive and dysregulated inflammatory host reactions to infection and thus contribute to high virus pathogenicity.
Indexed as
Identifiers
What OpenQuestion holds
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.