Getah virus triggers ROS-mediated autophagy in mouse Leydig cells

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 13, 2025

Introduction Getah virus (GETV) is a zoonotic transmitted via mosquito-vertebrate cycle. While previous studies have explored the epidemiology and pathogenicity of GETV in various species, its molecular mechanisms remain largely unexplored. Methods This study investigated impact infection associated on reactive oxygen species (ROS) autophagy levels mouse Leydig cells both vivo vitro . The male mice TM3 were treatment with N-acetylcysteine (NAC) to reduce cellular ROS levels. Rapamycin (Rapa) 3-Methyladenine (3- MA) used change infected uninfected cells. Results Discussion findings revealed that testes speciffcally targeted induced oxidative stress while enhancing testicular tissue. Using as an model, confirmed replication this cell line, triggering increased Treatment markedly reduced tissue GETV. Interestingly, use rapamycin led cells, no signiffcant alterations These results indicate elevates levels, subsequently inducing We also found plays important role replication. When using NAC 3-MA, corresponding decrease TCID 50 was observed. Conversely, upregulation Rapa resulted increase Therefore, we speculate may exploit pathway facilitate ffndings illuminate interplay between host providing valuable insights for therapeutic strategies targeting infections.

Language: Английский

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Infectious viruses and neurodegenerative diseases: The mitochondrial defect hypothesis

Reviews in Medical Virology, Journal Year: 2024, Volume and Issue: 34(4)

Published: June 21, 2024

Abstract Global attention is riveted on neurodegenerative diseases due to their unresolved aetiologies and lack of efficacious therapies. Two key factors implicated include mitochondrial impairment microglial ageing. Several viral infections, including Herpes simplex virus‐1 (HSV‐1), human immunodeficiency virus (HIV) Epstein‐Barr virus, are linked heightened risk these disorders. Surprisingly, numerous studies indicate viruses induce aforementioned precipitating events. Hepatitis C Virus, HIV, respiratory syncytial HSV‐1, Japanese Encephalitis Zika Enterovirus 71 specifically impact function, leading malfunction. These vital organelles govern various cell activities and, under specific circumstances, trigger This article explores the role infections in elucidating pathogenesis ailments. Various instigate ageing via destruction, causing senescent microglia exhibit activated behaviour, thereby inducing neuroinflammation contributing neurodegeneration.

Language: Английский

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Activation of cGAS-STING signaling pathway during HCV infection

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Abstract Hepatitis C virus (HCV) is a major global health issue, infecting over 170 million people worldwide and leading to severe liver diseases, including cirrhosis hepatocellular carcinoma. The ability of HCV persist cause chronic infection partly due its evasion the host’s innate immune responses, particularly those mediated by RIG-I-MAVS pathway, which critical for antiviral defense. Studies have shown crucial role genome sensing DNA viruses cyclic GMP-AMP synthase (cGAS) followed cGAMP production activation downstream effector STING (stimulator interferon genes) induce IFN-β, however it not understood in RNA specially infection. In this study, we explored first time mechanism cGAS-STING pathway context infection, specifically using JFH-1 strain (genotype 2a). We observed that cGAS expression significantly upregulated during early second messenger (cGAMP), turn activates STING. This results significant induction type I interferon-β (IFN-β), essential mounting an effective response. Moreover, our demonstrated translocation with cellular organelles such as endoplasmic reticulum (ER) mitochondria. suggests intricately linked other signaling networks detecting responding Furthermore, knockdown experiments targeting cGAS, RIG-I revealed these proteins play suppressing replication, underscoring their potential therapeutic targets. These findings provide valuable insights into molecular mechanisms mediating response against HCV. Understanding pathway’s defense opens up new possibilities strategies aimed at enhancing immunity potentially developing treatments

Language: Английский

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AKT/mTOR mediated autophagy contributes to the self-replication of canine influenza virus in vivo and in vitro

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111648 - 111648

Published: Feb. 1, 2025

Language: Английский

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Circular RNA Vav3 mediated ALV-J inhibition of autophagy by modulating the gga-miR-375/CIP2A axis and activating AKT

Poultry Science, Journal Year: 2025, Volume and Issue: 104(4), P. 104923 - 104923

Published: Feb. 17, 2025

Avian leukosis virus subgroup J (ALV-J) is an immunosuppressive neoplastic virus, the growth retardation and performance of chickens after infection. Circular RNAs (circRNAs) play a crucial role in various types cancer. In previous study, we showed that circ-Vav3 was significantly elevated tumor livers avian leukosis-infected chickens. Autophagy essential cellular process, circRNAs have been confirmed to be key players autophagy regulation. this demonstrated overexpression inhibited autophagy. Specifically, functions as sponge for gga-miR-375, resulting increased expression CIP2A, which target gene gga-miR-375. turn, hinders fusion autophagosomes with lysosomes, leading incomplete autophagic flux, consequently, inhibition Further study gga-miR-375 inhibits CIP2A promotes by downregulating p-AKT. Additionally, treated cells rapamycin induce then cotransfected them The results cotransfection Moreover, exhibited further ALV-J infection, suggesting involved inhibiting caused infection through regulation gga-miR-375/CIP2A/AKT. conclusion, our gga-miR-375/CIP2A/AKT pathway mediated suppression ALV-J-induced

Language: Английский

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The Essential Role of Mitochondrial Dynamics in Viral Infections

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1955 - 1955

Published: Feb. 24, 2025

Mitochondria are dynamic organelles that play crucial roles in energy production, metabolic balance, calcium homeostasis, apoptosis, and innate immunity, key determinants of cell fate. They also targets for viral invasion the body. Many proteins target mitochondria, controlling mitochondrial morphology, metabolism, immune response, thereby achieving evasion, promoting their proliferation, accelerating infection process. Mitochondrial quality control is to maintaining normal physiological functions homeostasis. Dysregulation dynamics closely related development many diseases. New constantly being discovered. Viruses change by targeting mitochondria achieve a persistent state infection. Currently, understanding during limited. Research on impact provides foundation investigating pathogenesis infections, disease process, identifying potential therapeutic targets. This review focuses connection between priority areas research virus-mediated insight into regulation viruses explores means mitochondrial-mediated treatment

Language: Английский

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Design and Synthesis of New HCV NS3/4A Protease Inhibitors to Effective Against Drug Resistance

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 142087 - 142087

Published: March 1, 2025

Language: Английский

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The Emerging Roles of Vacuolar-Type ATPase-Dependent Lysosomal Acidification in Cardiovascular Disease

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 525 - 525

Published: April 3, 2025

The vacuolar-type ATPase (V-ATPase) is a multi-subunit enzyme complex that maintains lysosomal acidification, critical process for cellular homeostasis. By controlling the pH within lysosomes, V-ATPase contributes to overall homeostasis, helping maintain balance between degradation and synthesis of components. Dysfunction impairs leading accumulation undigested materials contributing various diseases, including cardiovascular diseases (CVDs) like atherosclerosis myocardial disease. Furthermore, V-ATPase's role in function suggests potential therapeutic strategies targeting this mitigate disease progression. Understanding mechanisms by which influences pathology essential developing novel treatments aimed at improving outcomes patients with heart vascular diseases.

Language: Английский

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Vital Role of PINK1/Parkin-Mediated Mitophagy of Pulmonary Epithelial Cells in Severe Pneumonia Induced by IAV and Secondary Staphylococcus aureus Infection

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4162 - 4162

Published: April 27, 2025

Influenza A virus (IAV) infection causes considerable morbidity and mortality worldwide, the secondary bacterial further exacerbates severity fatality of initial viral infection. Mitophagy plays an important role in host resistance to pathogen immune response, while its on pulmonary epithelial cells with co-infection remains unclear. The present study reveals that Staphylococcus aureus significantly increased loads human lung (A549) during H1N1 Meanwhile, S. triggered more intense mitophagy A549 by activating PINK1/Parkin signaling pathway. Notably, could contribute proliferation pathogens via inhibition cell apoptosis. Furthermore, based influenza infected mouse model, we showed activation was conducive bacteria lungs, aggravated inflammatory damage severe pneumonia at same time, eventually decreased survival rate. results elucidated effect related molecular mechanism following IAV for first which will provide valuable information pathogenesis virus/bacteria interaction new ideas treatment pneumonia.

Language: Английский

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Immune mechanism of n-butanol extract of Clerodendrum bungei against loach infected with Aeromonas hydrophila

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 1, 2025

Traditional Chinese medicines (TCMs) have a wide variety of chemical components and biological activities, which are applied in multiple fields such as medicine, agriculture food. Clerodendrum bungei (C. bungei), known "ChouMuDan" Chinese, is traditional herb belonged to the shrub genus used treat various diseases. Previous studies indicated C. had certain activity antimicrobial aspects, therefore, present study focus on exploring its antibacterial effect loaches infected with A. hydrophila mechanism. This first prepared n-butanol extract bungei, using relux extraction liquid-liquid organic partition method. Then, loach was randomly divided into two groups. After experiment, livers from different groups were dissected for microRNA sequencing. The samples sequenced Hiseq Single-End mode obtain original data. Unique Reads aligned non-coding RNA sequences Rfam 13 database Blast screen out RNAs identify their types numbers further analysis functions regulatory mechanisms. Count value miRNA calculated, expression data conserved each sample sorted out. Finally, seven differentially expressed that regulate immunity, selected verify credibility identified by Two libraries mCK1 mC4 constructed, mode, Steud. (BECB) hydrophila. Differentially miRNAs identified, among 9 up-regulated 17 down-regulated. cluster showed pattern changed significantly after BECB treatment. KEGG enrichment carried target genes, top 30 most enriched pathways p-value. result suggested immune-related mTOR signaling pathway RIG-I-like receptor may critical resistance infection treatment, together RT-qPCR results. In this study, related carbohydrate lipid metabolism 24 h, be because proliferation differentiation immune cells require large number nutrients provide energy. indicates pathogens did not appear until exposure h. infection, both autophagy activated promote cells, induce production type I IFN inflammatory factors, then trigger innate specific immunity. These findings could basis research development agents based application biopesticides aquaculture, especially farming.

Language: Английский

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