Anti-SARS-CoV-2 Small Molecule Targeting of Oxysterol-Binding Protein (OSBP) Activates Cellular Antiviral Innate Immunity DOI Creative Commons
Subramaniyan Bharathiraja,

Emily C. Falcon,

A. Moore

et al.

ACS Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Human oxysterol-binding protein (OSBP) is a potentially druggable mediator in the replication of broad spectrum positive-sense (+) single-stranded RNA (ssRNA) viruses, including members Picornaviridae, Flaviviridae, and Coronaviridae. OSBP cytoplasmic lipid transporting capable moving cholesterol phosphoinositides between endoplasmic reticulum (ER) Golgi, ER lysosome. Several structurally diverse antiviral compounds have been reported to function through targeting OSBP, natural product compound OSW-1. Our prior work shows that transient OSW-1 treatment induces reduction levels over multiple successive cell generations (i.e., multigenerational), with no apparent cellular toxicity, OSW-1-induced has activity against (+)ssRNA viruses. This study extends these findings establishes vitro pathogenic human rhinovirus (HRV1B), feline coronavirus peritonitis virus (FIPV), 229E (HCoV-229E), severe acute respiratory syndrome 2 (SARS-CoV-2). We also demonstrate airway epithelial cells alters expression innate immune mediators, interferon (IFN) related genes IFNB1, IFNL3, CXCL10, ISG15, MX1. Furthermore, enhances induction specific components type I III IFN responses triggered by viral mimetic polyinosinic-polycytidylic acid (Poly IC). In summary, this further demonstrates importance presents as potential regulator responses.

Language: Английский

cGAS-like receptors drive a systemic STING-dependent host response in Drosophila DOI Creative Commons

Xianlong Ai,

Huimin Deng, Xiaoyan Li

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(12), P. 115081 - 115081

Published: Dec. 1, 2024

cGAS-like receptor (cGLR)-stimulator of interferon genes (STING) recently emerged as an important pathway controlling viral infections in invertebrates. However, its exact contribution at the organismal level remains uncharacterized. Here, we use STING::GFP knockin reporter Drosophila flies to document activation vivo. Four tissues strongly respond injection cyclic dinucleotide 3'2'- guanosine monophosphate-adenosine monophosphate (cGAMP): central nervous system, midgut, Malpighian tubules, and genital ducts. The pattern induction injected with 3'2'-cGAMP or infected by two viruses different tropism suggests that is induced a systemic signal produced virus-infected cells. Accordingly, ectopic expression cGLR2 fat body induces STING signaling remote cGLR1/2-dependent activity transferred females during mating. Furthermore, infection can alter sleep cGLR1/2- STING-dependent manner. Altogether, our results reveal host response Drosophila.

Language: Английский

Citations

5
Role of HIF in fish inflammation DOI
Xiaowei Shi, Feng Gao, Xianliang Zhao

et al.

Fish & Shellfish Immunology, Journal Year: 2023, Volume and Issue: 143, P. 109222 - 109222

Published: Nov. 12, 2023

Language: Английский

Citations

11
Mucosal Immunity against SARS-CoV-2 in the Respiratory Tract DOI Creative Commons

Hae-Eun Noh,

Min‐Seok Rha

Pathogens, Journal Year: 2024, Volume and Issue: 13(2), P. 113 - 113

Published: Jan. 26, 2024

The respiratory tract, the first-line defense, is constantly exposed to inhaled allergens, pollutants, and pathogens such as viruses. Emerging evidence has demonstrated that coordination of innate adaptive immune responses in tract plays a crucial role protection against invading pathogens. Therefore, better understanding mucosal immunity airways critical for development novel therapeutics next-generation vaccines severe acute syndrome coronavirus 2 (SARS-CoV-2) other Since disease 2019 pandemic, our knowledge expanded. In this review, we describe latest regarding key components system tract. addition, summarize host upper lower following SARS-CoV-2 infection vaccination, discuss impact allergic airway inflammation on SARS-CoV-2.

Language: Английский

Citations

3
Fish cells persistently infected with nervous necrosis virus produce a small-molecule substance for reducing cellular metabolism and suppressing viral multiplication DOI Creative Commons
Han Sol Lee,

Toyohiko Nishizawa

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

Language: Английский

Citations

0
Types I to IV IFNs and their receptors in white spotted bamboo shark (Chiloscyllium plagiosum) DOI

Yu Hang Deng,

Bo Li, Shan Nan Chen

et al.

Developmental & Comparative Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 105338 - 105338

Published: Feb. 1, 2025

Language: Английский

Citations

0
ORMDL3 restrains type-I interferon signaling and anti-tumor immunity by promoting RIG-I degradation DOI Open Access
Qi Zeng,

Yao Chen,

Shimeng Zhang

et al.

Published: Feb. 20, 2025

Mounting evidence has demonstrated the genetic association of ORMDL3 (ORMDL Sphingolipid Biosynthesis Regulator 3) gene polymorphisms with bronchial asthma and a diverse set inflammatory disorders. However, its role in type I interferon (IFN) signaling remains poorly defined. Herein, we report that is negative modulator IFN by interacting MAVS (Mitochondrial Antiviral Signaling protein) subsequently promoting proteasome-mediated degradation RIG-I (Retinoic Acid-Inducible Gene I). Immunoprecipitation coupled mass spectrometry (IP-MS) assays uncovered binds to USP10 (Ubiquitin-Specific Protease 10), which forms complex stabilizes through decreasing K48-linked ubiquitination. thus disrupts interaction between RIG-I, thereby degradation. Additionally, subcutaneous syngeneic tumor models C57BL/6 mice revealed inhibition enhances anti-tumor efficacy augmenting proportion cytotoxic CD8 positive T cells production microenvironment (TME). Collectively, our findings reveal pivotal roles maintaining antiviral innate immune responses immunity.

Language: Английский

Citations

0
ISGylation: is our genome yearning for such a modification? DOI Creative Commons
Zheng Chen, Zheng Li, Ying Wang

et al.

Acta Biochimica et Biophysica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

ISGylation is the post-translational modification of protein substrates covalently conjugated with ubiquitin-like protein, interferon-stimulated gene 15 (ISG15). Although initially linked to antiviral immunity, recent evidence highlights important roles for in various biological processes, such as maintaining genomic stability, promoting tumourigenesis, and being involved other pathological conditions. In this review, we examine molecular mechanisms underlying ISGylation, its interplay modifications, involvement diverse processes. We propose future research directions advance field discuss how might be harnessed ensure human health, particularly genome instability-associated diseases.

Language: Английский

Citations

0
Petroselinic Acid from Apiaceae Family Plants Ameliorates Autoimmune Disorders Through Suppressing Cytosolic-Nucleic-Acid-Mediated Type I Interferon Signaling DOI Creative Commons

Yue Guo,

Yunying Wang, Yao Wang

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 329 - 329

Published: Feb. 24, 2025

The recognition of cytosolic nucleic acids is a critical step in the host immune response against danger signals, such as molecular patterns from pathogens or tissue damage. Nonetheless, over-reactivity to self-nucleic leads sustained production type I interferon (IFN), mediated either by cGAS RLR, contributing pathogenesis certain autoimmune diseases, Aicardi–Goutières syndrome (AGS). Therefore, inhibiting excessive IFN represents potential therapeutic strategy for conditions. In this study, we discovered that petroselinic acid (PA), natural compound isolated Apiaceae family plants, effectively suppresses induced acids. Mechanistic investigations revealed PA inhibits phosphorylation TBK1 and IRF3, which are key nodal proteins within pathway. Notably, docking suggests binding between sensors, RIG-I. Moreover, found attenuates expression their downstream interferon-stimulated genes (ISGs) models AGS disease characterized accumulation. Thus, our research identifies offers promising treating diseases resulting aberrant hyperactivation interferon.

Language: Английский

Citations

0
Autophagy and Respiratory Viruses: Mechanisms, Viral Exploitation, and Therapeutic Insights DOI Creative Commons
Farnaz Aligolighasemabadi,

Estera Bakinowska,

Kajetan Kiełbowski

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 418 - 418

Published: March 12, 2025

Respiratory viruses, such as influenza virus, rhinovirus, coronavirus, and respiratory syncytial virus (RSV), continue to impose a heavy global health burden. Despite existing vaccination programs, these infections remain leading causes of morbidity mortality, especially among vulnerable populations like children, older adults, immunocompromised individuals. However, the current therapeutic options for viral are often limited supportive care, underscoring need novel treatment strategies. Autophagy, particularly macroautophagy, has emerged fundamental cellular process in host response infections. This not only supports homeostasis by degrading damaged organelles pathogens but also enables xenophagy, which selectively targets particles degradation enhances defense. viruses have evolved mechanisms manipulate autophagy pathways, using them evade immune detection promote replication. review examines dual role manipulation defense, focusing on complex interplay between autophagy-related pathways. By elucidating mechanisms, we aim highlight potential targeting enhance antiviral responses, offering promising directions development effective treatments against

Language: Английский

Citations

0
Molecular mechanisms in DYT-PRKRA: pathways regulated by PKR activator protein PACT DOI Creative Commons

Tricia A. Simon,

Rekha C. Patel

Dystonia, Journal Year: 2025, Volume and Issue: 4

Published: March 13, 2025

Dystonia- PRKRA (DYT- ), previously termed dystonia 16 (DYT16), is a movement disorder which currently has very limited treatments available and no cure. To develop effective therapeutic options, it essential to characterize the underlying pathophysiology identify potential drug targets. This review summarizes recent studies that shed light on molecular mechanisms involved in DYT- pathogenesis. gene encodes for protein PACT (Protein Activator of Protein Kinase R) individuals with mutations early-onset generalized dystonia. While precise linking neuronal etiology remain incompletely understood, research indicates such cause dysregulation signaling pathways cellular stress response as well production antiviral cytokines interferons (IFNs). focuses effect known functions PACT.

Language: Английский

Citations

0