Recent advances in ZBP1-derived PANoptosis against viral infections

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 16, 2023

Innate immunity is an important first line of defense against pathogens, including viruses. These pathogen- and damage-associated molecular patterns (PAMPs DAMPs, respectively), resulting in the induction inflammatory cell death, are detected by specific innate immune sensors. Recently, Z-DNA binding protein 1 (ZBP1), also called DNA-dependent activator IFN regulatory factor (DAI) or DLM1, reported to regulate death as a central mediator during viral infection. ZBP1 interferon (IFN)-inducible gene that contains two Z-form nucleic acid-binding domains (Zα1 Zα2) N-terminus receptor-interacting homotypic interaction motifs (RHIM1 RHIM2) middle, which interact with other proteins RHIM domain. By sensing entry RNA, induces PANoptosis, protects host cells infections, such influenza A virus (IAV) herpes simplex (HSV1). However, some viruses, particularly coronaviruses (CoVs), induce PANoptosis hyperactivate system, leading cytokine storm, organ failure, tissue damage, even death. In this review, we discuss mechanism ZBP1-derived pro-inflammatory cytokines influence double-edged sword results cell. Understanding may be critical for improving therapeutic strategies.

Язык: Английский

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Pregnancy-specific responses to COVID-19 revealed by high-throughput proteomics of human plasma

Communications Medicine, Год журнала: 2023, Номер 3(1)

Опубликована: Апрель 4, 2023

Pregnant women are at greater risk of adverse outcomes, including mortality, as well obstetrical complications resulting from COVID-19. However, pregnancy-specific changes that underlie such worsened outcomes remain unclear.Plasma samples were collected pregnant and non-pregnant individuals (male female) with (n = 72 pregnant, 52 non-pregnant) without 29 41 COVID-19 patients grouped asymptomatic, mild, moderate, severe, or critically ill according to NIH classifications. Proteomic profiling 7,288 analytes corresponding 6,596 unique protein targets was performed using the SOMAmer platform.Herein, we profile plasma proteome controls show alterations display a dose-response relationship disease severity; yet, proteomic perturbations dampened during pregnancy. In both state, response induced by shows enrichment mediators implicated in cytokine storm, endothelial dysfunction, angiogenesis. Shared identified: tailored may protect conceptus heightened inflammation, while stronger repel infection. Furthermore, can accurately identify patients, even when asymptomatic mild symptoms.This study represents most comprehensive characterization patients. Our findings emphasize distinct immune modulation between states, providing insight into pathogenesis potential explanation for more severe observed women.Pregnant increased experiencing compared general population. reasons this still unclear. We measured proteins present blood these healthy individuals. found some COVID-19-associated lower levels women, which could help fetus harmful body’s natural While affected shared others distinctly only group.

Язык: Английский

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Neurobiological Alterations Induced by SARS-CoV-2: Insights from Variant-Specific Host Gene Expression Patterns in hACE2-Expressing Mice

Viruses, Год журнала: 2025, Номер 17(3), С. 329 - 329

Опубликована: Фев. 27, 2025

Since the onset of COVID-19 pandemic, various severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants have emerged. Although primary site SARS-CoV-2 infection is lungs, it can also affect brain and induce neurological symptoms. However, specific effects different on remain unclear. In this study, a whole-transcriptome analysis was conducted using tissues K18-hACE2 mice infected with ancestral B.1 (Wuhan) variant major concern, including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) B.1.529 (Omicron). After sequencing, differential gene expression, ontology (GO) genome pathway enrichment analyses were performed. An Immune Cell Abundance Identifier (ImmuCellAI) used to identify abundance cell populations. Additionally, RT-qPCR validate RNA-seq data. The viral load hierarchical clustering divided samples into two clusters notable differences in expression at day 6 post-infection for all compared control group. GO Kyoto Encyclopedia genes genomes revealed similar patterns variants. ImmuCellAI changes immune populations, decrease CD4+ T B proportions increase CD8+ dendritic proportions. A co-expression network that some genes, such as STAT1, interleukin-6 (IL-6) tumor necrosis factor alpha (TNF-α), dysregulated IL-6, CXCL10 IRF7 further validated analysis. conclusion, study provides, first time, an extensive transcriptome mouse after

Язык: Английский

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K18- and CAG-hACE2 Transgenic Mouse Models and SARS-CoV-2: Implications for Neurodegeneration Research

Molecules, Год журнала: 2022, Номер 27(13), С. 4142 - 4142

Опубликована: Июнь 28, 2022

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that might lead to very serious consequences. Notably, mental status change, brain confusion, and smell taste disorders along with neurological complaints have been reported in patients infected SARS-CoV-2. Furthermore, human tissue autopsies from COVID-19 show the presence of SARS-CoV-2 neuroinvasion, which correlates manifestation meningitis, encephalitis, leukocyte infiltration, neuronal damage. The olfactory mucosa has suggested as way entry into brain. infection also known provoke hyper-inflammatory reaction an exponential increase production pro-inflammatory cytokines leading systemic responses, even absence direct cells. Angiotensin-converting enzyme (ACE2), receptor SARS-CoV-2, extensively demonstrated be present periphery, neurons, glial cells different regions. To dissect details complications develop therapies helping survivors regain pre-infection quality life, development robust clinical models highly warranted. Several angiotensin-converting (hACE2) transgenic mouse developed used for antiviral drug screening vaccine development, well better understanding molecular pathogenetic mechanisms infection. In this review, we summarize recent results studies involving two such models, namely K18- CAG-hACE2 transgenics, evaluate indirect impact on central nervous system.

Язык: Английский

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Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Сен. 12, 2023

The central nervous system (CNS) influences the immune generally by regulating systemic concentration of humoral substances (e.g., cortisol and epinephrine), whereas peripheral (PNS) communicates specifically with according to local interactions/connections. An imbalance between components PNS might contribute pathogenesis further development certain diseases. In this review, we have explored "thread" (hardwiring) connections primary/secondary/tertiary lymphoid tissues/organs) sensory, sympathetic, parasympathetic, enteric systems (ENS)) in health disease

Язык: Английский

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Deciphering the molecular mechanisms of Maxing Huoqiao Decoction in treating pulmonary fibrosis via transcriptional profiling and circRNA-miRNA-mRNA network analysis

Phytomedicine, Год журнала: 2023, Номер 115, С. 154754 - 154754

Опубликована: Март 12, 2023

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung condition with unknown etiology and high mortality. Chinese herbal medicine has been used for more than thousand years to treat various diseases.The current study aimed examine whether Maxing Huoqiao Decoction (MXHQD) exerts therapeutic effects on IPF further uncover its underlying molecular mechanisms.Mouse model of acute injury (ALI) or was induced by intratracheal instillation LPS bleomycin, respectively. ALI mice were treated MXHQD 7 days, tissues taken test after modeling 24 h. gavaged 21 days modeling. Lung subjected whole transcriptome detection, the differential RNAs experimentally verified.The results showed that alleviated computed tomography (CT) pathological degree changes in IPF, improved expression related genes reduced hydroxyproline mice. also decreased cell numbers bronchoalveolar lavage fluids, levels inflammatory factors significantly inhibited. By applying analysis, acted 40 mRNAs, 15 miRNAs, 25 novel lncRNAs 17 circRNAs resist fibrosis. The competing endogenous RNA (ceRNA) network diagram multiple components against through targets. mRNAs mainly innate immune response defense virus. Then mRNA-miRNA-differential circRNA tissue verified. ZBP1 ISG15 system anti virus verified at both gene protein expressions. could inhibit elevation model.Overall, our findings provide compelling evidence can alleviate modulating immunity. This first reveal mechanism multi-components, multi-channels multi-targets anti-IPF MXHQD, supports potential clinical application IPF.

Язык: Английский

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Viral-induced neuronal necroptosis: Detrimental to brain function and regulation by necroptosis inhibitors

Biochemical Pharmacology, Год журнала: 2023, Номер 213, С. 115591 - 115591

Опубликована: Май 16, 2023

Язык: Английский

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A cell-adapted SARS-CoV-2 mutant, showing a deletion in the spike protein spanning the furin cleavage site, has reduced virulence at the lung level in K18-hACE2 mice.

Virology, Год журнала: 2024, Номер 592, С. 109997 - 109997

Опубликована: Янв. 28, 2024

Here we investigated the virulence properties of a unique cell-adapted SARS-CoV-2 mutant showing ten-amino acid deletion encompassing furin cleavage site spike protein (Δ

Язык: Английский

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Upregulation of Neuroinflammation-Associated Genes in the Brain of SARS-CoV-2-Infected Mice

Pathogens, Год журнала: 2024, Номер 13(7), С. 528 - 528

Опубликована: Июнь 22, 2024

Neurological manifestations are a significant complication of coronavirus disease 2019 (COVID-19), but the underlying mechanisms yet to be understood. Recently, severe acute respiratory syndrome 2 (SARS-CoV-2)-induced neuroinvasion and encephalitis were observed in K18-hACE2 mice, leading mortality. Our goal this study was gain insights into molecular pathogenesis neurological mouse model. To analyze differentially expressed genes (DEGs) brains mice following SARS-CoV-2 infection, we performed NanoString gene expression analysis using three individual animal samples at 1, 3, 6 days post-infection. We identified DEGs by comparing them animals that not infected with virus. found upregulated day post-infection mainly associated Toll-like receptor (TLR) signaling, RIG-I-like (RLR) cell death pathways. However, downregulated neurodegeneration synaptic signaling In correlation profiles, multiplexed immunoassay showed upregulation multiple cytokines chemokines involved inflammation SARS-CoV-2-infected brains. Furthermore, pathway indicated possible link between TLR2-mediated pathways neuroinflammation, as well pyroptosis necroptosis brain. conclusion, our work demonstrates neuroinflammation-associated which can provide key insight COVID-19 patients.

Язык: Английский

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ZBP1 and heatstroke

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 10, 2023

Heatstroke, which is associated with circulatory failure and multiple organ dysfunction, a heat stress-induced life-threatening condition characterized by raised core body temperature central nervous system dysfunction. As global warming continues to worsen, heatstroke expected become the leading cause of death globally. Despite severity this condition, detailed mechanisms that underlie pathogenesis still remain largely unknown. Z-DNA-binding protein 1 (ZBP1), also referred as DNA-dependent activator IFN-regulatory factors (DAI) DLM-1, was initially identified tumor-associated interferon (IFN)-inducible protein, but has recently been reported be Z-nucleic acid sensor regulates cell inflammation; however, its biological function not yet fully understood. In present study, brief review main regulators presented, in ZBP1 significant factor regulating pathological characteristics through ZBP1-dependent signaling. Thus, lethal mechanism revealed, addition second other than nucleic sensor.

Язык: Английский

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