TLR4 signalling: the key to controlling EV71 replication and inflammatory response

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: June 13, 2024

Hand, foot, and mouth disease (HFMD) is a common infectious caused by enterovirus 71 (EV71) that frequently affects children, leading to severe infections in some cases. In general, when infection occurs, the body upregulates inflammatory responses eliminate pathogenic microorganisms protect host from infection. However, EV71 may inhibit host's innate immunity promote virus At present, it not fully understood how hijack cells for its own replication. Toll-like receptor 4 (TLR4), natural immune receptor, historically associated with bacterial endotoxin-induced responses. still unclear whether TLR4 altered during this study, we observed reduction both protein gene transcript levels RD, GES-1, Vero following infection, as detected RT-qPCR, immunofluorescence staining western blot. Furthermore, downstream molecules of MYD88, p-NF-κB p65, p-TBK1 related cytokines were also reduced, suggesting antiviral response suppressed. To determine impact changes on interfered EV71-infected RD agonist or inhibitor results showed activation inhibited replication, while inhibition Besides, replication was promoted siRNA-transfected cells. This suggests down-regulation expression can defense self-replication. novel mechanism be strategy evade immunity.

Language: Английский

---

Coordination Polymer Nanozymes Suppress TLR4-Mediated Inflammatory Cytokine Production

ACS Applied Nano Materials, Journal Year: 2024, Volume and Issue: 7(15), P. 17786 - 17794

Published: July 30, 2024

Excessive inflammation can cause severe damage to biological tissues and organs, current anti-inflammatory drugs still have certain limitations. This study aims explore strategies. Nanozymes, a class of nanomaterials with enzyme-like catalytic properties, gained significant attention in recent years. In this study, iron ion integrated coordination polymer nanodots (FNDs) were synthesized. The effects FNDs investigated from multiple aspects, including material characterization, antioxidant performance testing, vitro cell experiments, mouse model experiments. results demonstrated that the characteristics small size, high stability, excellent capacity. experiments showed significantly inhibited production LPS-induced TNF-α, IL-1β, IL-6 THP-1 macrophages. Further analysis signaling pathways revealed markedly suppressed NF-κB MAPK downregulated expression TLR4 CD14 on surface Experiments models indicated cellular organs such as lungs liver, reduced number inflammatory cells concentrations peripheral blood. demonstrates possess providing strategy for treatment diseases.

Language: Английский

---

Engineering a broad-spectrum multi-epitope vaccine to combat emerging monkeypox virus by immunoinformatic approaches

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Monkeypox virus (MPXV), has caused 41,664 confirmed cases and five deaths in non-endemic regions, as reported by the World Health Organization (WHO). There is an urgent demand for effective vaccines to combat prevent spread of MPXV. Traditional vaccine development low-throughput, expensive, time-consuming, susceptible reversion virulence. As alternative, a reverse vaccinology approach can be employed promising tool design safe against Here, MPXV proteins associated with viral infection were analyzed potential immunogenic epitopes multi-epitope constructs based on B-cell, CD4+, CD8+ epitopes. Epitopes selected allergenicity, antigenicity, toxicity parameters. The prioritized then combined via peptide linkers N-terminally fused various protein adjuvants, including PADRE, beta-defensin 3, 50S ribosomal L7/12, RS-09, cholera toxin B subunit (CTB). All further computationally validated physicochemical properties, antigenicity potential, safety, solubility, structural stability. three-dimensional structure construct was also predicted. Moreover, molecular docking dynamics (MD) simulations between TLR-4 immune receptor demonstrated strong stable interaction. codon-optimized high expression E. coli platform finally cloned silico into pET21a(+) vector. Collectively, these results could represent innovative tools formulation transformative other infectious diseases.

Language: Английский

---

A myeloid differentiation–like protein in partnership with Toll5 from the pest insect Spodoptera litura senses baculovirus infection

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(44)

Published: Oct. 23, 2024

Many types of viruses infect insects and other arthropods. In contrast, little is known about how arthropods sense viruses, although several innate immune pathways including Toll have antiviral functions. Large DNA in the family Baculoviridae are used to control a number pest insects. Here, we studied Spodoptera litura Autographa californica multiple nucleopolyhedrovirus (AcMNPV) test hypothesis that one or more myeloid differentiation–like (ML) proteins members baculoviruses. We identified 11 ML 12 genes S. genome. A series experiments indicated protein (SlML-11) binds budded form AcMNPV partners with Toll5 (SlToll5). SlML-11 also bound sphingomyelin (SPM), which component virion envelope. Disabling SlToll5 increased susceptibility infection, while priming larvae SPM reduced as measured by survival adult stage clearance from individuals emerged adults. conclude pathogen-associated molecular pattern molecule interact function recognition receptor senses AcMNPV.

Language: Английский

---

Immunoinformatic approach to design T cell epitope-based chimeric vaccine targeting multiple serotypes of dengue virus

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 19

Published: Nov. 28, 2024

The global dengue outbreak is a significant public health concern, with the World Health Organization recording over 3 million cases and 0.04% case fatality rate until July 2023. infection anticipated to rise in vulnerable regions worldwide. While live-attenuated vaccines are current standard, their effectiveness certain populations debated. Furthermore, presence of four closely related virus serotypes can lead antibody-dependent enhancement, compromising vaccine efficacy. In response, we propose development therapeutic subunit-vaccine based on epitopes from all induce robust cross-protective cellular immunity. Our approach involves designing multi-epitope chimeric immunogen using envelope protein virus. MHC-I MHC-II binding T-cell were selected antigen processing criteria. most potent immunodominant for each serotype, considering immunogenicity, population coverage, prediction scores, combined AAY linker peptides create stable polypeptide. Predicted be both antigenic non-allergenic, design exhibits soluble tertiary structure half-life 4.4 h mammalian systems. addition, employed an agonist toll-like receptor-4 at N-terminal downstream immunostimulatory validated through docking molecular dynamics simulations. This construct shows promise eliciting effective immune response against serotypes.

Language: Английский

---