2026-08-13 | 'Mismatched' Ebola vaccine may soon be rolled out widely.
Opinions shift after new data suggest vaccine for Ebola Zaire may also protect against Bundibugyo.
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2026-07-28 | Fever Temperatures Differentially Alter Ebola-Antibody Functionality Depending on Affinity Maturation 2306819
Abstract Introduction In 2013-16, Western Africa experienced the largest known outbreak of the highly lethal virus, Ebolavirus (EBOV) and ongoing sporadic outbreaks have occurred since. EBOV is the causative agent of EBOV hemorrhagic fever, characterized by a high-grade fever. Antibody responses to EBOV have been correlated with protection against EBOV disease. However, it is unclear how antibody functions result in protection from repeat exposure. Understanding antibody-mediated mechanisms of protection against Ebola infection is critical to maximize long-term protection against infection. Methods We utilize a systems serology approach to analyze a cohort of 60 survivors of the 2013-16 Ebola epidemic in Guinea and 81 individuals of pygmy ancestry in the Republic of Congo who did not have documented EBOV infection, but do experience frequent zoonotic exposures to characterize the impact of fever conditions on affinity matured EBOV-directed antibody responses. Antibody binding and cellular activation were measured at both physiologic (37C) and high grade fever (40C) temperatures. Results We show that neutralization of EBOV is impaired under fever temperatures, both for affinity-matured and non-specific antibody responses. In contrast, effector-mediated functions, particularly against the EBOV soluble glycoprotein (sGP, a signature previously linked to enhanced protection in animal vaccine challenge models), are enhanced at febrile temperatures. This temperature-sensitive enhancement of effector function correlates with full length GP and sGP-directed IgG subclasses, IgA, FcγR-binding- and FcαR-binding antibodies, demonstrating a highly associated network of humoral features that are maintained during periods of febrile temperatures. Conclusion Collectively, our findings suggest that although neutralization plays a key role in surveillance in a non-fever state, fever modulates affinity-matured antibody responses to the hemorrhagic fever-inducing EBOV, moving antibody profiles to a pro-effector function phenotype. Funding Source NIH NIAID U19 AI135995 Topic Categories Viral Immunology (VIR)
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2026-07-28 | PTPN13 Contributes to Ebola Virus-Induced Immune Dysregulation via Dephosphorylation of IRF3 and PI3K-p85.
Ebola virus disease (EVD) is characterized by immune dysregulation and damaging hyperinflammation. We aimed to characterize the signaling pathways and regulatory mechanisms dysregulated during EVD. To avoid hyperinflammation, innate immune signaling is regulated by post-translational modifications (PTMs), including protein phosphorylation. Here, we show that the protein tyrosine phosphatase nonreceptor type 13 (PTPN13) negatively regulates Interferon (IFN)-β while also positively regulating the neutrophil chemoattractant CXCL1. Using vectors encoding IRF3 with mutations on phosphorylation sites, we identified Y292 on IRF3 as a PTPN13 target of dephosphorylation. Knockout of PTPN13 increased IRF3 phosphorylation and expression of IFNβ and IFN-stimulated genes (ISGs) following poly(I:C) stimulation. Intriguingly, depletion of PTPN13 during Ebola virus (EBOV) infection resulted in decreased IFNβ and ISG induction at later time points post-infection, which correlated with increased viral titers. We identified PTPN13-mediated dephosphorylation of the viral protein VP35 as one potential mechanism inhibiting virus replication. Additionally, the induction of inflammatory chemokines, including CXCL1, decreased in PTPN13 knockout cells late during EBOV infection. These effects could be explained by increased phosphorylation of the regulatory p85 subunit of PI3K. Dephosphorylation of p85 promotes its degradation, subsequently enhancing PI3K kinase activity and downstream signaling via AKT. Together, our study suggests that PTPN13 is involved in immune regulation and efficient antiviral responses by dephosphorylation of IRF3, EBOV-VP35 and PI3K-p85.
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2026-07-17 | Ebola virus exploits host lncRNA LINC01740 to enhance ATF3 and suppress antiviral immune responses.
Ebola virus (EBOV) infection causes severe hemorrhagic fever marked by dysregulated cytokine production, impaired antiviral defenses, and multi-organ failure. Macrophages are primary targets of EBOV, and viral replication profoundly alters macrophage transcriptional programs, driving hyperinflammation. Although long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of immunity and viral pathogenesis, their roles in EBOV infection remain poorly understood. We performed comprehensive transcriptomic profiling of primary human monocyte-derived macrophages infected with the highly pathogenic EBOV Mayinga variant. Infection triggered extensive remodeling of both coding and non-coding transcriptomes, including hundreds of differentially expressed lncRNAs. Functional analysis of neighboring protein-coding genes of EBOV-induced lncRNAs (EVILs) revealed enrichment of pathways linked to cytokine signaling, transcriptional regulation, and cell signaling, all of which are central to Ebola virus disease (EVD) pathogenesis. Among the most strongly induced EVILs, LINC01740 and its neighboring protein-coding gene, Activating Transcription Factor 3 (ATF3), were significantly upregulated. Antisense oligonucleotide-mediated inhibition of LINC01740 reduced ATF3 mRNA and protein levels. CRISPR/Cas13d-mediated knockdown of ATF3 restored type I interferon (IFN-I) signaling and antiviral gene expression in EBOV-infected macrophages. Mechanistically, ATF3 functions as a negative regulator of IFN-I and type I interferon-stimulated gene expression, thereby suppressing antiviral immune responses in EBOV-infected macrophages. Together, these findings identify a previously unrecognized LINC01740-ATF3-IFN-I regulatory axis that EBOV exploits to promote immune suppression and viral replication.
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2026-07-17 | AI-Driven Discovery and BSL-4 Validation of Cross-Filovirus Ebola-Marburg Inhibitors and their Synergistic Combinations.
Filovirus outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV), pose severe global health threats characterized by high rates of fatal hemorrhagic fever. While species-specific vaccines and therapeutic monoclonal antibodies are approved for Zaire ebolavirus, broadly-active therapeutics remain unavailable, leaving populations vulnerable to MARV and other pathogenic Ebola species, such as Bundibugyo (BDBV) and Sudan (SUDV) ebolaviruses. Here we report a computationally guided, infectious virus validated screening platform for the rapid discovery of broad-spectrum filovirus antivirals. By leveraging quantitative structure- activity relationship (QSAR) models, we screened 142,382 compounds in silico to prioritize 125 high-potential candidates. Subsequent dose-response and viability profiling identified 23 compounds exhibiting potent, low-micromolar pan-filovirus activity and favorable cytotoxicity profiles. Molecular docking indicates these compounds target conserved structural and functional domains-primarily the VP35 and L proteins-which may disrupt essential viral replication and immune antagonism. Furthermore, systematic combinatorial screening revealed three highly synergistic compound pairs, notably NCGC00113249-01 and NCGC00118008-01, demonstrating robust cross-species efficacy. By targeting conserved vulnerabilities across the filovirus family, this integrated in silico and in vitro pipeline provides a scalable framework to rapidly nominate and optimize synergistic therapeutic regimens against both endemic and emerging viral threats including BDBV.
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