The segmented flavivirus Alongshan virus reduces mitochondrial mass via degrading STAT2 to suppress innate immune response DOI Creative Commons
Yinghua Zhao,

Liyan Sui,

Mingming Pan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 7, 2024

Abstract Alongshan virus (ALSV) is a newly discovered pathogen of the Flaviviridae family, characterized by multi-segmented genome distantly related to canonical flaviviruses. Understanding pathogenic mechanism emerging segmented flavivirus crucial for development intervention strategies. Here we show that ALSV can infect multiple mammalian cells and induces expression antiviral genes. Moreover, sensitive IFN-β possesses ability counteract type I IFN response. Mechanistically, ALSV’s nonstructural protein NSP1 binds degrades human STAT2 through an autophagy pathway in species-dependent manner, resulting direct inhibition interferon-stimulated genes (ISGs). Specifically, methyltransferase domain key sites F175/R176 located coiled-coil STAT2. NSP1-mediated degradation results reduction mitochondrial mass disrupting dynamics induce mitophagy inhibiting biogenesis, thereby suppressing innate immune Interestingly, using 3-Methyladenine enhancing biogenesis PPARγ agonist pioglitazone reverse ISGs, suggesting promoting presents effective strategy. Our findings elucidate intricate regulatory crosstalk between host’s response, providing valuable insights into pathogenesis strategy flavivirus.

Language: Английский

Role of extracellular vesicles in the pathogenesis of mosquito-borne flaviviruses that impact public health DOI Creative Commons
Pedro Pablo Martínez-Rojas,

Verónica Monroy-Martínez,

Blanca H. Ruíz-Ordaz

et al.

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 4, 2025

Abstract Mosquito-borne flaviviruses represent a public health challenge due to the high-rate endemic infections, severe clinical outcomes, and potential risk of emerging global outbreaks. Flavivirus disease pathogenesis converges on cellular factors from vectors hosts, their interactions are still unclear. Exosomes microparticles extracellular vesicles released cells that mediate intercellular communication necessary for maintaining homeostasis; however, they have been shown be involved in establishment progression. This review focuses roles mosquito-borne flavivirus diseases: how contribute viral cycle completion, cell-to-cell transmission, responses such as inflammation, immune suppression, evasion, well use biomarkers or therapeutics (antiviral vaccines). We highlight current findings concerning functionality different models dengue virus, Zika yellow fever Japanese encephalitis West Nile virus infections diseases. The available evidence suggests diverse functions between constituting novel effectors understanding pathogenic mechanisms flaviviral

Language: Английский

Citations

1
Alteration of mitochondrial function in arthropods during arboviruses infection: a review of the literature DOI Creative Commons
María E. Santana-Román, Santos Ramírez-Carreto, Paola Maycotte

et al.

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

Published: Feb. 13, 2025

Arthropods serve as vectors for numerous arboviruses responsible diseases worldwide. Despite their medical, veterinary, and economic significance, the interaction between arthropods remains poorly understood. Mitochondria in play a crucial role by supplying energy cell survival viral replication. Some can replicate within arthropod without harming host. Successful transmission depends on efficient replication vector’s tissues, ultimately reaching salivary glands to vertebrate host, including humans, via blood-feeding. This review summarizes current knowledge of mitochondrial function during arbovirus infection, highlighting gaps compared studies mammals other pathogens relevant arthropods. It emphasizes processes insects that require further investigation uncover mechanisms underlying arthropod-borne transmission.

Language: Английский

Citations

1
Non-cytopathic bovine viral diarrhea virus (BVDV) inhibits innate immune responses via induction of mitophagy DOI Creative Commons
Zhijun Li, Ying Zhang,

Bao Zhao

et al.

Veterinary Research, Journal Year: 2024, Volume and Issue: 55(1)

Published: March 5, 2024

Abstract Bovine viral diarrhea virus (BVDV) belongs to the genus Pestivirus within family Flaviviridae . Mitophagy plays important roles in virus-host interactions. Here, we provide evidence that non-cytopathic (NCP) BVDV shifts balance of mitochondrial dynamics toward fission and induces mitophagy inhibit innate immune responses. Mechanistically, NCP triggers translocation dynamin-related protein (Drp1) mitochondria stimulates its phosphorylation at Ser616, leading fission. In parallel, BVDV-induced complete via Parkin-dependent pathway contributes eliminating damaged MAVS- mtDNA-cGAS-mediated immunity responses, mtROS-mediated inflammatory responses apoptosis initiation. Importantly, demonstrate LIR motif E RNS is essential for induction. conclusion, this study first show a central role promoting cell survival inhibiting vitro.

Language: Английский

Citations

7
Infectious viruses and neurodegenerative diseases: The mitochondrial defect hypothesis DOI

Tianshi Jiang,

Kaili Zhu,

Gloria Kang

et al.

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

Citations

4
Duck Tembusu virus induced mitophagy in vacuolate spermatogenic cells is mediated by PINK1-Parkin pathway DOI Creative Commons
Yufei Huang, Xiaoman Yan,

Xiaoya Chu

et al.

Poultry Science, Journal Year: 2025, Volume and Issue: 104(2), P. 104795 - 104795

Published: Jan. 14, 2025

As a significant emerging and re-emerging pathogen in China, the widely spread of Duck Tembusu virus (DTMUV) caused enormous economic losses to poultry industry. On account DTMUV diseases' main symptoms on haemorrhagic oophoritis, intensive attentions were focused female reproductive organ. Nevertheless, infection sperm testis manifested that was an important vector for vertical transmission DTMUV. In present study, histopathology, immunofluorescence electron microscopy (TEM) analysis DTMUV-infected duck revealed induced seminiferous epithelium injury via spermatogenic cells vacuolization. After infection, expression autophagy-related genes proteins significantly up-regulated. Further TEM discovered different stages autophagic mitophagy structures visible cytoplasm after infection. And more notably, testicular protein PINK1 Parkin increased summary, our study that, PINK1-Parkin pathway mediated activated then

Language: Английский

Citations

0
The Essential Role of Mitochondrial Dynamics in Viral Infections DOI Open Access
Xujie Duan, Rui Liu, Wenjun Lan

et al.

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

Citations

0
IGF2BP1 Enhances Neprilysin mRNA Stability to Promote Proliferation, Invasion, and Angiogenesis in Placental Trophoblasts DOI Creative Commons
Chunhai Fan, Huanjiao Jenny Zhou, Yan Pan

et al.

International Journal of General Medicine, Journal Year: 2025, Volume and Issue: Volume 18, P. 967 - 980

Published: Feb. 1, 2025

Preeclampsia (PE) is a severe gestational disorder characterized by sudden hypertension and proteinuria, with substantial risks to both mother fetus. This study aims delineate the role of neprilysin, metalloprotease known for its in modulating vasoactive peptides, pathophysiology PE. We recruited cohort 57 participants, comprising 38 patients diagnosed PE 19 healthy controls, matched demographic clinical characteristics. Neprilysin expression was assessed serum placental tissues through quantitative RT-qPCR Western blot analyses. Functional impacts neprilysin modulation were explored via siRNA knockdown overexpression HTR8/SVneo cells, followed assessments oxidative stress, mitochondrial function, apoptosis, trophoblast invasion using various biochemical assays including CCK-8, DCFH-DA, JC-1 staining, flow cytometry. Our results demonstrate marked compared controls. Elevated levels positively correlated increased systolic diastolic blood pressures. In functional assays, alleviated H2O2-induced restored improved cell migration EVT cells. Conversely, IGF2BP1, regulator mRNA stability, exacerbated intensified cellular damage under stress conditions. The reciprocal regulation IGF2BP1 highlights critical molecular interplay impacting resilience These findings establish as mediator pathogenesis PE, where aberrant linked hypertensive symptoms impaired function. interaction between provides potential therapeutic target mitigating progression suggesting avenues future intervention strategies.

Language: Английский

Citations

0
Icarisid Ⅱ modulates mitochondrial dynamics for anti-HBV activity DOI Creative Commons

Zhengyun Liu,

Haiyan Yang,

Juan Wen

et al.

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

Published: April 1, 2025

To investigate the potential anti-hepatitis B virus (HBV) activity of Icariside Ⅱ (ICS Ⅱ), and elucidate its underlying mitochondrial dynamics mechanisms. The study employed in vivo vitro assays to evaluate anti-HBV effects ICS Ⅱ. An HBV replicating mouse model was established through hydrodynamic injection pAAV/HBV1.2, impact on replication liver toxicity assessed. In cell-based used HBV-positive HepG2.2.15 cells. Cytotoxicity determined with CCK-8 assay, while ELISA qPCR were measure HBsAg, HBeAg, DNA levels. livers II-treated HBV-infected mice taken for transcriptome sequencing screen different genes, results verified by Western Blot. Mitochondrial morphology visualized using confocal imaging transmission electron microscopy. Key protein expressions related fission fusion analyzed via WB. Intracellular ROS generation assessed fluorescence staining. found that exhibited significant both vitro. RNA-Seq indicated modulated mRNA levels Fisl, a associated dynamics, during response. It induced fragmentation enhanced motility Notably, key proteins demonstrated alterations favoring fission. Furthermore, effectively reduced production exhibits regulation production.

Language: Английский

Citations

0
Mitochondrial Oxidative Phosphorylation in Viral Infections DOI Creative Commons
Neeraja Purandare,

Esha Ghosalkar,

Lawrence I. Grossman

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(12), P. 2380 - 2380

Published: Dec. 4, 2023

Mitochondria have been identified as the “powerhouse” of cell, generating cellular energy, ATP, for almost seven decades. Research over time has uncovered a multifaceted role mitochondrion in processes such stress signaling, precursor molecules, immune response, and apoptosis to name few. Dysfunctional mitochondria resulting from departure homeostasis results degeneration. Viruses hijack host cell machinery facilitate their own replication absence bonafide machinery. Replication being an energy intensive process necessitates regulation oxidative phosphorylation occurring at electron transport chain generate energy. Mitochondria, therefore, can be attractive therapeutic target by limiting viral replication. In this review we focus on physiology limited studies highlighting regulatory effects viruses induce chain.

Language: Английский

Citations

10
Crosstalk between Dysfunctional Mitochondria and Proinflammatory Responses during Viral Infections DOI Open Access

Zitao Sun,

Yanjin Wang, Xin Jin

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9206 - 9206

Published: Aug. 24, 2024

Mitochondria play pivotal roles in sustaining various biological functions including energy metabolism, cellular signaling transduction, and innate immune responses. Viruses exploit metabolic synthesis to facilitate viral replication, potentially disrupting mitochondrial subsequently eliciting a cascade of proinflammatory responses host cells. Additionally, the disruption membranes is involved regulation. During infections, mitochondria orchestrate through generation reactive oxygen species (ROS) release DNA, which serves as an effective defense mechanism against virus invasion. The targeting damage may represent novel approach antiviral intervention. This review summarizes regulatory underlying response induced by during providing new insights for strategies.

Language: Английский

Citations

3