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

Treatment of COVID‐19‐Associated Ageusia and Xerostomia DOI
Hironori Tsuchiya

Oral Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Language: Английский

Citations

0
Ectonucleotidases DOI
Raíssa Leite-Aguiar, Marco De Giorgi, Luiz Eduardo Baggio Savio

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Citations

0
Exploring HIV-1 Maturation: A New Frontier in Antiviral Development DOI Creative Commons
Aidan McGraw,

Grace Hillmer,

Stefania M. Medehincu

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(9), P. 1423 - 1423

Published: Sept. 6, 2024

HIV-1 virion maturation is an essential step in the viral replication cycle to produce infectious virus particles. Gag and Gag-Pol polyproteins are assembled at plasma membrane of virus-producer cells bud from it extracellular compartment. The newly released progeny virions initially immature noninfectious. However, once polyprotein cleaved by protease virions, mature capsid proteins assemble form fullerene core. This core, harboring two copies genomic RNA, transforms morphology into morphological transformation referred as maturation. Virion influences distribution Env glycoprotein on surface induces conformational changes necessary for subsequent interaction with CD4 receptor. Several host factors, including like cyclophilin A, metabolites such IP6, lipid rafts containing sphingomyelins, have been demonstrated influence review article delves processes recruitment, emphasis role cell factors environmental conditions. Additionally, we discuss microscopic technologies assessing development current antivirals specifically targeting this critical replication, offering long-acting therapeutic options.

Language: Английский

Citations

3
Research Advances on the Role of Lipids in the Life Cycle of Human Coronaviruses DOI Creative Commons
Cuiling Ding, Yibo Chen,

Miao Gen

et al.

Microorganisms, Journal Year: 2023, Volume and Issue: 12(1), P. 63 - 63

Published: Dec. 28, 2023

Coronaviruses (CoVs) are emerging pathogens with a significant potential to cause life-threatening harm human health. Since the beginning of 21st century, three highly pathogenic and transmissible CoVs have emerged, triggering epidemics posing major threats global public enveloped viruses encased in lipid bilayer. As fundamental components cells, lipids can play an integral role many physiological processes, which been reported important roles life cycle CoVs, including viral entry, uncoating, replication, assembly, release. Therefore, research on CoV provide basis for better understanding infection mechanism targets development new antiviral strategies. In this review, advances different stages possible that interfere discussed.

Language: Английский

Citations

5
Sequestration of membrane cholesterol by cholesterol-binding proteins inhibits SARS-CoV-2 entry into Vero E6 cells DOI Creative Commons
Magdalena Kulma, Aleksandra Šakanović, Apolonija Bedina-Zavec

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 716, P. 149954 - 149954

Published: April 16, 2024

Membrane lipids and proteins form dynamic domains crucial for physiological pathophysiological processes, including viral infection. Many plasma membrane proteins, residing within enriched with cholesterol (CHOL) sphingomyelin (SM), serve as receptors attachment entry of viruses into the host cell. Among these, human coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), use associated initial binding internalization. We hypothesized that interaction lipid-binding CHOL in could sequestrate thus affect efficiency virus cells, preventing steps have prepared CHOL-binding high affinities mammalian cells. Binding perfringolysin O domain four (D4) its variant D4E458L to impaired internalization receptor-binding SARS-CoV-2 spike protein pseudovirus complemented protein. replication Vero E6 cells was also decreased. Overall, our results demonstrate integrity CHOL-rich accessibility play an essential role cell entry.

Language: Английский

Citations

1
Serum lipidome reveals lipid metabolic dysregulation in severe fever with thrombocytopenia syndrome DOI Creative Commons
Shuai Guo, Yunjun Yan, Jingyao Zhang

et al.

BMC Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 14, 2024

Severe fever with thrombocytopenia syndrome (SFTS) is a rapidly progressing infectious disease high fatality rate caused by novel bunyavirus (SFTSV). The role of lipids in viral infections well-documented; however, the specific alterations lipid metabolism during SFTSV infection remain elusive. This study aims to elucidate metabolic dysregulations early stages SFTS patients. prospectively collected peripheral blood sera from 11 critical patients, 37 mild and 23 healthy controls for lipidomics analysis. A systematic bioinformatics analysis was conducted three aspects integrating differential expressions, correlations, lipid-clinical indices correlations reveal serum dysregulation SFTSV-infected individuals. Our findings significant Specifically, compared controls, patients exhibited distinct modes expression: increased levels including phosphatidylserine (PS), hexosylceramide (HexCer), triglycerides (TG); decreased lysophosphatidylcholine (LPC), acylcarnitine (AcCa), cholesterol esters (ChE); showing "dual changes" phosphatidylcholine (PC) phosphatidylethanolamine (PE). Finally, based on pathways literature analysis, we systematically elucidated potential mechanisms underlying stage infection. presents first global lipidome profile reveals patterns These provide new basis diagnosis, treatment, further investigation disease.

Language: Английский

Citations

1
Preliminary Study on the Restoration of the Phospholipid Profile in Serum from Patients with COVID-19 by Treatment with Vitamin E DOI Open Access
Marí­a Elena Soto, Linaloe Manzano-Pech, Verónica Guarner‐Lans

et al.

Published: June 10, 2024

SARS-CoV-2 is an obligatory intracellular pathogen that requires of a lipid bilayer membrane for its transport, to build nucleocapsid envelope and fuse with the host cell. The biological membranes are constituted by phospholipids (PLs) vitamin E (Vit E) protects them from oxidative stress (OS). aim this study was demonstrate if treatment Vit restores modified profile FA in PLs serum patients coronavirus disease-19 (COVID-19). We evaluated E, total fatty acids (TFA), acid (FAPL), (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 6-keto-PGF1α), interleukin-6 (IL-6) C-reactive protein (CRP) 22 COVID-19 before after compared values those 23 healthy subjects (HS). showed decrease TPLs, FAPL TFA comparison HS (p≤0.01) restored their levels (p≤0.04). Likewise, there increase IL-6 CRP (p≤0.001) decreased (p≤0.001). Treatment contributes restore infection leads OS inflammatory process.

Language: Английский

Citations

1
Lower serum LDL-C levels are associated with poor prognosis in severe fever with thrombocytopenia syndrome: a single-center retrospective cohort study DOI Creative Commons
Shuai Guo, Qing Dong,

Zhang Mao-mei

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: June 24, 2024

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease triggered by a novel bunyavirus (SFTSV). Characterized fever, thrombocytopenia, leukocytopenia, and multiple organ dysfunction manifestations, its primary mode of transmission through tick bites. Despite the critical role lipid metabolism in viral infections, lipids SFTS remains unclear. Methods This retrospective study analyzed 602 patients treated at Shandong Public Health Clinical Center from January 2021 to December 2023. Based on endpoint events, were classified into survival (S) death (D) groups. The S group was further non-critical (non-C) (C) groups based symptoms. All followed up for least 28 days after admission. Propensity score matching, multivariable logistic regression, analysis, time trend mediation analysis conducted assess association between LDL-C levels prognosis SFTS. Results serum admission significantly lower D C than non-C regression models indicated potential poor restricted cubic spline showed unidirectional mortality, cutoff value 1.59 mmol/L. revealed higher earlier mortality low-LDL-C high-LDL-C group. trends over post-admission that gradually increased SFTS, favorable prognosis. Finally, low are associated hepatic, cardiac, coagulation functions. Conclusion Low potentially

Language: Английский

Citations

1
Increased viperin expression induced by avian infectious bronchitis virus inhibits viral replication by restricting cholesterol synthesis: an in vitro study DOI Creative Commons
Yu Zhang,

T Zhang,

Yan-Peng Lu

et al.

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

Published: Sept. 27, 2024

Language: Английский

Citations

1
EFR3A: a new raft domain organizing protein? DOI Creative Commons

Magdalena Trybus,

Anita Hryniewicz‐Jankowska, Karolina Wójtowicz

et al.

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: Oct. 25, 2023

Membrane rafts play a crucial role in the regulation of many important biological processes. Our previous data suggest that specific interactions flotillins with MPP1 are responsible for membrane raft domain organization and erythroid cells. Interaction flotillin-based protein network components underlies mechanism formation regulation, including cells low expression MPP1.We sought to identify other flotillin partners via immobilized recombinant flotillin-2-based affinity approach mass spectrometry technique. The results were further confirmed immunoblotting co-immunoprecipitation. In order study effect candidate on physicochemical properties plasma membrane, gene was knocked down siRNA, fluorescence lifetime imaging microscopy spot-variation correlation spectroscopy employed.EFR3A identified as interacts flotillin-2. Moreover, this newly discovered interaction demonstrated overlay assay using EFR3A is stable component detergent-resistant fraction HeLa cells, its presence sensitive removal cholesterol. While silencing gene, we observed decreased living or giant vesicles derived from altered mobility probe, indicated spectroscopy. found disturb epidermal growth factor receptor phospholipase C gamma phosphorylation affect factor-dependent cytosolic Ca2+ concentration.Altogether, our hitherto unreported flotillin-2-EFR3A interaction, which might be regulation. This implies participation multiple cellular processes, those connected cell signaling points possible human health, particular cancer biology.

Language: Английский

Citations

3