SARS-CoV-2 entry and fusion are independent of ACE2 localization to lipid rafts DOI
William Bolland,

I. Maréchal,

Chloé Petiot

et al.

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

Published: July 16, 2024

ABSTRACT Membrane fusion occurs at the early stages of SARS-CoV-2 replication, during entry virus, and later formation multinucleated cells called syncytia. Fusion is mediated by binding viral Spike protein to its receptor ACE2. Lipid rafts are dynamic nanodomains enriched in cholesterol sphingolipids. Rafts can act as platforms for dìerent viruses localizing virus receptors, attachment factors same membrane microdomains. Here, we first demonstrate that depletion methyl-beta-cyclodextrin inhibits entry. To further study role ACE2 lipid raft localization entry, design a GPI-anchored construct. Both ACE2-GPI proteins similarly expressed plasma membrane. Through flotation assays, show cell lines, localises predominantly domains while non-raft associated. We then compare ability permit pseudovirus syncytia replication variants. find little dìerence two proteins. Our results dependent raft-independent process. IMPORTANCE often exploited used enhance their into or spread from cell-to-cell. The cell-to-cell poorly understood. function studied through disruption cholesterol-depleting agents. However, this process may have ò-target impacts on independently lipid-raft disruption. Therefore, created an construct localizes using GPI anchor. Conversely, wild-type was does not modify dynamics SARS-CoV-2.

Language: Английский

Lipid Raft Integrity and Cellular Cholesterol Homeostasis Are Critical for SARS-CoV-2 Entry into Cells DOI Open Access
Ahmed Bakillah,

Fatimah Al Hejji,

Abdulrahman Almasaud

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(16), P. 3417 - 3417

Published: Aug. 19, 2022

Lipid rafts in cell plasma membranes play a critical role the life cycle of many viruses. However, involvement membrane cholesterol-rich lipid entry severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into target cells is not well known. In this study, we investigated whether presence microdomains required for SARS-CoV-2 host cells. Our results show that depletion cholesterol by methyl-beta-cyclodextrin (MβCD) treatment impaired expression surface receptor angiotensin-converting enzyme (ACE2), resulting significant increase The effects exerted MβCD could be substantially reversed exogenous replenishment. contrast, disturbance intracellular homeostasis statins or siRNA knockdown key genes involved biosynthesis and transport pathways reduced study also reveals SREBP2-mediated process These suggest cholesterol-enriched cellular are essential Pharmacological manipulation might provide new therapeutic strategies to alleviate

Language: Английский

Citations

41
SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147 DOI Creative Commons

Shaimaa Shouman,

Nada Elkholy,

Alaa E. Hussien

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 4, 2024

T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While indicates an active anti-viral response, is sign of poor prognosis. T-cells, essence, rarely express ACE2 receptors, making cause cell depletion enigmatic. Moreover, emerging strains posed immunological challenge, potentially alarming for next pandemic. Herein, we review how possible indirect direct key mechanisms could contribute SARS-CoV-2-associated-lymphopenia. The fundamental mechanism inflammatory cytokine storm elicited by viral infection, which alters host metabolism into more acidic state. This "hyperlactic acidemia" together suppresses T-cell proliferation triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results shift from steady-state hematopoiesis stress hematopoiesis. Even low expression, presence cholesterol-rich lipid rafts on activated T-cells may enhance entry syncytia formation. Finally, indicate participation other receptors or auxiliary proteins that can work alone concert mechanisms. Therefore, address CD147-a novel route-for its new variants. CD147 not only expressed but it interacts co-partners orchestrate various biological processes. Given these features, appealing candidate pathogenicity. Understanding molecular cellular behind SARS-CoV-2-associated-lymphopenia will aid discovery potential therapeutic targets improve resilience our immune system against this rapidly evolving virus.

Language: Английский

Citations

9
Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: New tricks for old dogs DOI Open Access
Egor V. Shekunov, Polina D. Zlodeeva, Svetlana S. Efimova

et al.

Antiviral Research, Journal Year: 2023, Volume and Issue: 212, P. 105575 - 105575

Published: March 2, 2023

Language: Английский

Citations

19
Lipid Rafts: The Maestros of Normal Brain Development DOI Creative Commons

Barbara Viljetić,

Senka Blažetić, Irena Labak

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 362 - 362

Published: March 18, 2024

Lipid rafts, specialised microdomains within cell membranes, play a central role in orchestrating various aspects of neurodevelopment, ranging from neural differentiation to the formation functional neuronal networks. This review focuses on multifaceted involvement lipid rafts key neurodevelopmental processes, including differentiation, synaptogenesis and myelination. Through spatial organisation signalling components, facilitate precise events that determine fate during embryonic development adulthood. The evolutionary conservation underscores their fundamental importance for structural complexity nervous system all species. Furthermore, there is increasing evidence environmental factors can modulate composition function influence processes. Understanding intricate interplay between neurodevelopment not only sheds light mechanisms governing brain but also has implications therapeutic strategies aimed at cultivating networks addressing disorders.

Language: Английский

Citations

7
Host Membranes as Drivers of Virus Evolution DOI Creative Commons

Mélanie Matveeva,

Marine Lefebvre,

Henri Chahinian

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(9), P. 1854 - 1854

Published: Aug. 31, 2023

The molecular mechanisms controlling the adaptation of viruses to host cells are generally poorly documented. An essential issue resolve is whether membranes, and especially lipid rafts, which usually considered passive gateways for many enveloped viruses, also encode informational guidelines that could determine virus evolution. Due their enrichment in gangliosides confer an electronegative surface potential, rafts impose a first control level favoring selection with enhanced cationic areas, as illustrated by SARS-CoV-2 variants. Ganglioside clusters attract viral particles dynamic electrostatic funnel, more population winning race. However, forces account only small part energy raft-virus interaction, depends mainly on ability form network hydrogen bonds raft gangliosides. This fine tuning virus-ganglioside interactions, stabilize membrane, generates second pressure driven typical induced-fit mechanism. Gangliosides play active role this process, wrapping around spikes through quicksand-like Viruses thus endless race access they bound evolve perpetually, combining speed (electrostatic potential) precision (fine amino acids) under selective immune system. Deciphering membrane evolution may open new avenues design innovative antivirals.

Language: Английский

Citations

13
Lipid Droplets: Formation, Degradation, and Their Role in Cellular Responses to Flavivirus Infections DOI Creative Commons

J. Hsia,

Dongxiao Liu,

L.W. Haynes

et al.

Microorganisms, Journal Year: 2024, Volume and Issue: 12(4), P. 647 - 647

Published: March 24, 2024

Lipid droplets (LDs) are cellular organelles derived from the endoplasmic reticulum (ER), serving as lipid storage sites crucial for maintaining homeostasis. Recent attention has been drawn to their roles in viral replication and interactions with viruses. However, precise biological functions of LDs pathogenesis remain incompletely understood. To elucidate interaction between viruses, it is imperative comprehend biogenesis dynamic other organelles. In this review, we explore intricate pathways involved LD biogenies within cytoplasm, encompassing uptake fatty acid nutrients facilitated by CD36-mediated membranous protein (FABP/FATP)-FA complexes, FA synthesis via glycolysis cytoplasm TCL cycle mitochondria. While primarily occurs ER, matured intricately linked multiple Viral infections can lead diverse consequences terms status cells post-infection, potentially involving breakdown through activation lipophagy. exact mechanisms underlying destruction or accumulation viruses elusive. The significance renders them effective targets developing broad-spectrum antivirals. Moreover, considering that reducing neutral lipids a strategy anti-obesity treatment, depletion may not pose harm cells. This presents promising antiviral therapeutics minimally non-toxic host.

Language: Английский

Citations

6
Role of lipoprotein structure and dynamics in disease development: from atherosclerosis to Covid-19 DOI Open Access

Correa Marcano Yubexi Yakari

Published: Jan. 1, 2023

Lipoproteins play a crucial role in lipid metabolism, serving as carriers for lipids such cholesterol and triglycerides the bloodstream. Atherosclerosis is complex cardiovascular disease characterized by accumulation of cholesterol-rich plaques arterial walls, leading to narrowed hardened arteries. Recently, spike protein from SARS-CoV-2 virus, responsible COVID-19, has been subject research concerning its potential impact on metabolism association with disease. Understanding interaction between lipoproteins influence could have implications our knowledge health. In this research, we investigated ultrastructure HDL individuals different profiles well mature model nascent membranes. these differences will help create novel rHDL particles superior lipid-removing CVD-treating properties. Finally, cell membranes study imbalances metabolism. To achieve objectives, deposition, exchange removal were followed techniques Neutron reflection attenuated total Fourier transformation infrared spectroscopy while, was unravelled small-angle X-ray scattering.

Language: Английский

Citations

10
The Preventive and Therapeutic Effects of Acute and Severe Inflammatory Disorders with Heparin and Heparinoid DOI Creative Commons
Ying Song,

Wu Yuxiang,

Fangfang Ding

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1078 - 1078

Published: Aug. 28, 2024

Systematic inflammatory response syndrome (SIRS) and the accompanying sepsis pose a huge threat to human health worldwide. Heparin is part of standard supportive care for disease. However, molecular mechanism not fully understood yet, potential signaling pathways that play key roles have yet been elucidated. In this paper, main findings regarding mechanisms associated with beneficial effects heparin, including inhibiting HMGB-1-driven inflammation reactions, histone-induced toxicity, thrombo-inflammatory control new emerging are concluded. To set up link between preclinical research clinical effects, outcomes trials summarized. Then, structure function relationship heparin discussed. By providing an updated analysis above results, paper highlights feasibility as possible alternative prophylaxis therapy.

Language: Английский

Citations

3
Key Factors in the Multiple Mechanisms of Virus Entry DOI Creative Commons
Yifan Wang,

Quanxiang Yu,

Shuru Lin

et al.

Published: Jan. 2, 2025

Review Key Factors in the Multiple Mechanisms of Virus Entry Yifan Wang 1,2, Quanxiang Yu 1,3, Shuru Lin Wenqi Jiang Zhengfei Qi 1,3,4, Lina Lian Wu Rui Ma Kexin Zhang Shurong Chen Jiayi Xie Lingli Zheng Min Zhou 1,3,4 and Qingshan Bill Fu 1,3,4,* 1 Shanghai Institute Materia Medica, Chinese Academy Sciences, 201203, China 2 School Life Science Medicine, Dalian University Technology, 124000, 3 Zhongshan for Drug Discovery, 528400, 4 Beijing 100049, * Correspondence: [email protected] Received: 22 October 2024; Revised: 12 November Accepted: 19 December Published: January 2025 Abstract: Viruses are non-cellular organisms that must parasitize multiply within living cells to achieve their replicative procedures. Viral assaults can affect bacteria, eukaryotes, archaea. Well-known viral illnesses human history include smallpox, Ebola, black death, Spanish flu, immunodeficiency virus (HIV), rabies, SARS, etc. Each these diseases has caused countless deaths severe consequences, greatly hindering progress civilization economic growth. Invasion host by viruses be broadly divided into several steps: adhesion, entry, replication, assembly, release. entry is particularly essential invasion cause infection. Different methods employed enveloped non-enveloped mediate entry. Whichever technique used, a few proteins (virus membrane cell receptor proteins) play crucial rules. Our knowledge structures important also since it inform us precise steps involved this procedure. This review discusses various (such as Clathrin/Caveolae-mediated endocytosis, Lipid raft, Macropinocytosis), lists typical fusion offers brief information on structural characteristics HIV recently discovered SARS-CoV-2. The intention page provide readers with an overall overview pathways serve theoretical foundation pertinent researches.

Language: Английский

Citations

0
Virally-initiated pain states: phenotype, mechanisms, and future directions DOI Creative Commons
Sara A. Dochnal, Steven P. Cohen, Mark R. Hutchinson

et al.

Frontiers in Pain Research, Journal Year: 2025, Volume and Issue: 6

Published: Jan. 28, 2025

The recent SARS-CoV-2 pandemic has underscored the significance of viral infections, affecting billions lives and costing trillions dollars globally. Even beyond SARS-CoV-2, common infections with viruses like influenza, HIV, herpesviruses have profound impacts their typical manifestations, often triggering acute chronic pain syndromes that can be life-altering. These virally induced states arise through direct replication within neurons, or indirectly, via immune responses to infection in both contexts afferent signaling dorsal root ganglion (DRG) subsequent higher order integration intracranial systems. Varicella-zoster virus (VZV), influenza virus, each provide a unique lens which examine interplay between activity pain. This perspective paper is not meant an exhaustive review virally-induced neuropathic states. It seeks explore curated aspects complexities these states, identify research gaps, suggest solutions using nanoscale molecular understanding psychoneuroimmunological biopsychosocial frameworks. Each subheading accompanied by list related issues for study we think will lead advances our vexing phenotype associated infection.

Language: Английский

Citations

0