Decoding dengue’s neurological assault: insights from single-cell CNS analysis in an immunocompromised mouse model DOI Creative Commons
Minyue Qiu,

Lixin Zhao,

Xiaojia Li

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: March 4, 2025

Dengue encephalitis, a severe neurological complication of dengue virus infection, is increasingly recognized for its rising incidence and significant public health burden. Despite growing prevalence, the underlying mechanisms effective therapeutic strategies remain poorly understood. Cellular atlas encephalitis was determined by single-nucleus RNA sequencing. Viral load level cytokines expression detected RT-qPCR. The target cells were verified immunofluorescence. cytotoxic effect CD8+ T cell flow cytometry, immunofluorescence, in vivo depletion, adoptive transfer CCK-8-based viability assay. Axonal synaptic reduction induced infection demonstrated RT-qPCR, Western blot, transmission electron microscope Finally, motor sensory functions mice open field test hot plate test, respectively. In this study, we utilized sequencing on brain tissues from dengue-infected murine model to construct comprehensive cellular encephalitis. Our findings identify neurons, particularly inhibitory GABAergic subtypes, as primary targets virus. Additionally, immune infiltration observed, contributing damage. Comprehensive analyses cell-cell communication, combined with depletion restoration experiments, have elucidated critical role triggering through their interaction neurons. These infiltrate peripheral circulation, interact induce damage synapse axon, accompanied dysfunction. We defined mouse identified neuron addition, cell, which leads apoptosis dysfunction mice. study provides molecular framework understanding advanced technologies. insights gained serve foundation future investigations into pathogenesis development targeted approaches.

Language: Английский

Severe dengue in the intensive care unit DOI Creative Commons
Alexandre Mestre Tejo,

Débora Toshie Hamasaki,

Letícia Mattos Menezes

et al.

Journal of Intensive Medicine, Journal Year: 2023, Volume and Issue: 4(1), P. 16 - 33

Published: Sept. 28, 2023

Dengue fever is considered the most prolific vector-borne disease in world, with its transmission rate increasing more than eight times last two decades. While cases present mild to moderate symptoms, 5% of patients can develop severe disease. Although mechanisms are yet not fully comprehended, immune-mediated activation leading excessive cytokine expression suggested as a cause main findings critical patients: increased vascular permeability that may shock and thrombocytopenia, coagulopathy induce hemorrhage. The risk factors include previous infection by different serotype, specific genotypes associated efficient replication, certain genetic polymorphisms, comorbidities such diabetes, obesity, cardiovascular World Health Organization recommends careful monitoring prompt hospitalization warning signs or propensity for reduce mortality. This review aims update diagnosis management dengue intensive care unit.

Language: Английский

Citations

30
Regulation and functions of the NLRP3 inflammasome in RNA virus infection DOI Creative Commons

Zhaoyang Yue,

Xuelong Zhang, Yu Gu

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 5, 2024

Virus infection is one of the greatest threats to human life and health. In response viral infection, host’s innate immune system triggers an antiviral mostly mediated by inflammatory processes. Among many pathways involved, nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome has received wide attention in context infection. The NLRP3 intracellular sensor composed three components, including NLRP3, adaptor apoptosis-associated speck-like containing CARD (ASC), cysteine protease caspase-1. After being assembled, can trigger caspase-1 induce gasdermin D (GSDMD)-dependent pyroptosis, promoting maturation secretion proinflammatory cytokines such as interleukin-1 (IL-1β) interleukin-18 (IL-18). Recent studies have revealed that a variety viruses activate or inhibit via particles, proteins, nucleic acids. this review, we present regulatory mechanisms functions upon RNA demonstrate multiple therapeutic strategies target for anti-inflammatory effects

Language: Английский

Citations

12
The Dynamic Landscape of Capsid Proteins and Viral RNA Interactions in Flavivirus Genome Packaging and Virus Assembly DOI Creative Commons

Anastazia Jablunovsky,

Joyce Jose

Pathogens, Journal Year: 2024, Volume and Issue: 13(2), P. 120 - 120

Published: Jan. 28, 2024

The Flavivirus genus of the Flaviviridae family enveloped single-stranded RNA viruses encompasses more than 70 members, many which cause significant disease in humans and livestock. Packaging assembly flavivirus genome is essential for formation virions, requires intricate coordination genomic RNA, viral structural, nonstructural proteins association with virus-induced, modified endoplasmic reticulum (ER) membrane structures. capsid (C) protein, a small but versatile RNA-binding positive are at heart elusive process. nucleocapsid core, consisting encapsidated by C proteins, buds through ER membrane, contains glycoproteins prM E organized as trimeric spikes into lumen, forming an immature virus. During maturation process, involves low pH-mediated structural rearrangement furin cleavage secretory pathway, spiky virus partially ordered core becomes smooth, mature no discernible nucleocapsid. This review focuses on mechanisms packaging examining functional aspects protein RNA. We current lexicon critical features evaluate interactions between context throughout life cycle.

Language: Английский

Citations

11
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
Characterization of Novel Plantaricin-Derived Antiviral Peptides Against Flaviviruses DOI Open Access
Abubakr A. M. Omer, Sanjiv Kumar, Robert Selegård

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1038 - 1038

Published: Jan. 25, 2025

Flaviviruses, including West Nile virus, Zika and Dengue pose global health challenges due to their distribution, pathogenicity, lack of effective treatments or vaccines. This study investigated the antiviral activity novel truncated peptides derived from two-peptide plantaricins PLNC8 αβ, PlnEF, PlnJK, PlnA. The potential was predicted using machine learning tools, followed by in vitro evaluation against Kunjin virus plaque reduction assays Vero cells. Molecular docking assessed peptide interactions with KUNV ZIKV. Full-length PlnA, PlnE, PlnF, PlnJ, PlnK demonstrated limited efficacy vitro, despite silico predictions suggesting for PlnJ. Large discrepancies were observed between experimentally determined activities. However, complementary PlnEF PlnJK exhibited significant synergistic effects. Furthermore, α1-15 β1-20 reduced viral load over 90%, outperforming full-length counterparts. revealed α β, variants, ZIKV, a mechanism involving envelope disruption. These findings highlight plantaricin-derived as promising candidates flaviviruses, warranting further investigation into mechanisms applications.

Language: Английский

Citations

1
Viral subversion of selective autophagy is critical for biogenesis of virus replication organelles DOI Creative Commons
Yun Lan,

Sophie Wilhelmina van Leur,

Julia Fernando

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 10, 2023

Abstract Infection by many (+)RNA viruses is accompanied ER-expansion and membrane remodelling to form viral replication organelles, followed assembly secretion of progenies. We previously identified that virus-triggered lipophagy was critical for flaviviral assembly, driven the lipid droplet associated protein Ancient ubiquitin 1 (Aup1). A conjugating Ube2g2 functions as a co-factor Aup1 host dependency factor in our study. Here we characterized its function: Ube2g2-deficient cells displayed dramatic reduction virus production, which could be rescued reconstituting wild-type but not catalytically deficient (C89K) mutant Ube2g2, suggesting enzymatic activity necessary. deficiency did affect entry particles resulted profound loss formation production infectious This phenomenon from dual (i) triggering conjunction with Aup1, (ii) degradation ER chaperones such Herpud1, SEL1L, Hrd1, along Sec62 restrict ER-phagy upon Xbp1-IRE1 triggered expansion. Our results therefore underscore an exquisite fine-tuning selective autophagy flaviviruses drive reorganization during infection enable biogenesis organelles.

Language: Английский

Citations

19
mRNA-encoded Cas13 can be used to treat dengue infections in mice DOI
Mausumi Basu, Chiara Zurla, Tabassum Tasnim Auroni

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(8), P. 2160 - 2172

Published: June 5, 2024

Language: Английский

Citations

6
Hijacking autophagy for infection by flaviviruses DOI Creative Commons
Minghui Song,

Yan Sun,

Xiao‐Bo Qiu

et al.

Virus Research, Journal Year: 2024, Volume and Issue: 347, P. 199422 - 199422

Published: June 20, 2024

Autophagy is a lysosomal degradative pathway, which regulates the homeostasis of eukaryotic cells. This pathway can degrade misfolded or aggregated proteins, clear damaged organelles, and eliminate intracellular pathogens, including viruses, bacteria, parasites. But, not all types viruses are eliminated by autophagy. Flaviviruses (e.g., Yellow fever, Japanese encephalitis, Hepatitis C, Dengue, Zika, West Nile viruses) single-stranded enveloped RNA transmitted to humans primarily through bites arthropods, leading severe widespread illnesses. Like coronavirus SARS-CoV-II, flaviviruses hijack autophagy for their infection escape from host immune clearance. Thus, it possible control these viral infections inhibiting In this review, we summarize recent research progresses on hijacking discuss feasibility antiviral therapies using inhibitors.

Language: Английский

Citations

5
The Japanese Encephalitis Antigenic Complex Viruses: From Structure to Immunity DOI Creative Commons
Baldeep Khare, Richard Kühn

Viruses, Journal Year: 2022, Volume and Issue: 14(10), P. 2213 - 2213

Published: Oct. 8, 2022

In the last three decades, several flaviviruses of concern that belong to different antigenic groups have expanded geographically. This has resulted in presence often more than one virus from a single group some areas, while Europe, Africa and Australia, additionally, multiple viruses belonging Japanese encephalitis (JE) serogroup co-circulate. Morphological heterogeneity dictates antibody recognition affects neutralization, which influences infection control. The latter is further impacted by sequential infections involving diverse co-circulating within region their cross-reactivity. ensuing complex molecular virus-host interplay leads either cross-protection or disease enhancement; however, determinants mechanisms driving these outcomes are unclear. this review, we provide an overview epidemiology four JE serocomplex viruses, parameters affecting flaviviral recognition, host immune responses current knowledge cross-reactivity differential clinical outcomes, may inform future preventative therapeutic interventions.

Language: Английский

Citations

22
Role of endoplasmic reticulum stress-related unfolded protein response and its implications in dengue virus infection for biomarker development DOI
Biswadeep Das, Sagnika Samal, Hamida Hamdi

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 329, P. 121982 - 121982

Published: July 28, 2023

Language: Английский

Citations

13