Integrin αvβ1 facilitates ACE2-mediated entry of SARS-CoV-2 DOI Creative Commons

Zeqiong Cai,

Han Bai,

Doudou Ren

et al.

Virus Research, Journal Year: 2023, Volume and Issue: 339, P. 199251 - 199251

Published: Nov. 2, 2023

Integrins have been suggested to be involved in SARS-CoV-2 infection, but the underlying mechanisms remain largely unclear. This study aimed investigate how integrins facilitate ACE2-mediated cellular entry of SARS-CoV-2. We first tested susceptibility a panel human cell lines infection using spike protein pseudotyped virus assay and examined expression levels these by qPCR, western blot flow cytometry. found that integrin αvβ1 was highly enriched susceptible lines. Additional studies demonstrated RGD (403-405)→AAA mutant defective binding compared its wild type counterpart, anti-αvβ1 antibodies significantly inhibited into cells. Further mouse NIH3T3 cells expressing ACE2, αv, β1, and/or suggest unable function as an independent receptor could SASR-CoV-2. Finally, we observed Omicron exhibited significant increase viral entry. Our findings may enhance our understanding pathogenesis offer potential therapeutic target for COVID-19.

Language: Английский

Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages DOI Creative Commons
Katja Hönzke, Benedikt Obermayer,

Christin Mache

et al.

European Respiratory Journal, Journal Year: 2022, Volume and Issue: 60(6), P. 2102725 - 2102725

Published: June 21, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis still elusive.Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied infected human lung explants adult stem cell derived organoids correlate related host factors with tropism, propagation, virulence compared SARS-CoV, influenza Middle East (MERS-CoV). Coronavirus disease 2019 (COVID-19) autopsy material was used validate ex vivo results.We provide evidence that expression must be considered scarce, thereby limiting propagation alveolus. Instead, lungs COVID-19 samples showed macrophages frequently positive for SARS-CoV-2. Single-cell/-nucleus transcriptomics further revealed nonproductive virus uptake a inflammatory anti-viral activation, especially "inflammatory macrophages", comparable those induced by SARS-CoV MERS-CoV, but different from NL63 infection.Collectively, our findings indicate severe injury probably results macrophage-triggered rather than viral of compartment.

Language: Английский

Citations

43
SARS-CoV-2 and the spike protein in endotheliopathy DOI Open Access
Luca Perico, Ariela Benigni, Giuseppe Remuzzi

et al.

Trends in Microbiology, Journal Year: 2023, Volume and Issue: 32(1), P. 53 - 67

Published: June 12, 2023

Language: Английский

Citations

36
Physiological Basis for Using Vitamin D to Improve Health DOI Creative Commons
Sunil J. Wimalawansa

Biomedicines, Journal Year: 2023, Volume and Issue: 11(6), P. 1542 - 1542

Published: May 26, 2023

Vitamin D is essential for life-its sufficiency improves metabolism, hormonal release, immune functions, and maintaining health. deficiency increases the vulnerability severity of type 2 diabetes, metabolic syndrome, cancer, obesity, infections. The active enzyme that generates vitamin [calcitriol: 1,25(OH)2D], CYP27B1 (1α-hydoxylase), its receptors (VDRs) are distributed ubiquitously in cells. Once calcitriol binds with VDRs, complexes translocated to nucleus interact responsive elements, up- or down-regulating expression over 1200 genes modulating physiological functions. Administration D3 correct metabolites at proper doses frequency longer periods would achieve intended benefits. While various tissues have different thresholds 25(OH)D concentrations, levels above 50 ng/mL necessary mitigate conditions such as infections/sepsis, reduce premature deaths. Cholecalciferol (D3) (not metabolites) should be used raise serum target concentration. In contrast, calcifediol [25(OH)D] raises concentrations rapidly agent choice emergencies infections, those who ICUs, insufficient hepatic 25-hydroxylase (CYP2R1) activity. maintain serum-ionized calcium concentration persons advanced renal failure hypoparathyroidism. Calcitriol is, however, ineffective most other conditions, including replacement therapy. Considering high costs higher incidence adverse effects due narrow therapeutic margins (ED50), 1α-vitamin analogs, 1α-(OH)D 1,25(OH)2D, not conditions. Calcifediol analogs cost 20 times more than D3-thus, they indicated a routine supplement hypovitaminosis D, osteoporosis, failure. Healthcare workers resist accepting inappropriate promotions, chronic osteoporosis infections-there no rationale doing so. Maintaining population's (above 40 ng/mL) supplements and/or daily sun exposure cost-effective way diseases sepsis, overcome viral epidemics pandemics, healthcare costs. Furthermore, overall health (hence reducing absenteeism), reduces cardiovascular decreases all-cause mortality, minimizes infection-related complications sepsis COVID-19-related hospitalizations Properly using illnesses costs: thus, it part clinical care.

Language: Английский

Citations

26
SARS-CoV-2 spike protein receptor binding domain promotes IL-6 and IL-8 release via ATP/P2Y2 and ERK1/2 signaling pathways in human bronchial epithelia DOI
Rui‐Gang Zhang, Xingjian Liu, Yuling Guo

et al.

Molecular Immunology, Journal Year: 2024, Volume and Issue: 167, P. 53 - 61

Published: Feb. 14, 2024

Language: Английский

Citations

9
TGFβ links EBV to multisystem inflammatory syndrome in children DOI Creative Commons
Carl Christoph Goetzke, Mona Massoud, Stefan Frischbutter

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

In a subset of children and adolescents, SARS-CoV-2 infection induces severe acute hyperinflammatory shock1 termed multisystem inflammatory syndrome in (MIS-C) at four to eight weeks after infection. MIS-C is characterized by specific T cell expansion2 systemic hyperinflammation3. The pathogenesis remains largely unknown. Here we show that impaired reactivation virus-reactive memory cells, which depends on increased serum levels the cytokine TGFβ resembling those occur during COVID-19 (refs. 4,5). This functional impairment reactivity accompanied presence TGFβ-response signatures B cells monocytes along with reduced antigen-presentation capabilities monocytes, can be reversed blocking TGFβ. Furthermore, receptor repertoires patients exhibit expansion expressing TCRVβ21.3, Epstein-Barr virus (EBV)-reactive clones capable eliminating EBV-infected cells. Additionally, trigger EBV reactivation, reversible blockade. Clinically, TGFβ-induced defect correlates higher seroprevalence compared age-matched controls, occurrence reactivation. Our findings establish connection between sequelae children, cytotoxicity triggered overproduction leads subsequent hyperinflammation.

Language: Английский

Citations

1
Trans-epithelial/endothelial electrical resistance (TEER): Current state of integrated TEER measurements in organ-on-a-chip devices DOI Creative Commons
Mridu Malik,

S. R. Steele,

Dipankar Mitra

et al.

Current Opinion in Biomedical Engineering, Journal Year: 2025, Volume and Issue: 34, P. 100588 - 100588

Published: March 20, 2025

Trans-epithelial/endothelial electrical resistance (TEER) is a non-invasive and quick method of assessing the integrity barrier tissues. Traditional TEER measurement methods such as chopstick electrode-based chamber-based work well with static, Transwell-based models; however, same do not directly apply to human on chip or organ-on-a-chip (OOC) platforms. With wide variety devices, innovative designs accurately measure TEER, without disturbing cells, are customized for various devices. Wire electrode integration, integrating two-probe four-probe technique, flexible printed circuit boards multi-electrode glass substrate-based some setups being utilized in conjunction OOC systems. The variability associated OOCs make standardization challenging; field working towards establishing guidelines acceptable values different constructs.

Language: Английский

Citations

1
Myocardial Oedema as a Consequence of Viral Infection and Persistence—A Narrative Review with Focus on COVID-19 and Post COVID Sequelae DOI Creative Commons
N Panagiotides, Michael Poledniczek, Martin Andreas

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(1), P. 121 - 121

Published: Jan. 14, 2024

Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic removal disturbed during pathological processes leading to inflammation, but also hypoxia or due alterations vascular perfusion coagulability. degradation of the glycocalyx as main component endothelial barrier well pericyte disintegration results accumulation interstitial intracellular water. Moreover, dysfunction evokes an increase metabolic waste products, cytokines inflammatory cells space contributing oedema formation. This leads stiffness impaired contractility, eventually resulting cardiomyocyte apoptosis, remodelling fibrosis. following article reviews pathophysiological including myocarditis, ischaemia-reperfusion injury viral infections with special focus on pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications potential long-term effects persistence (long COVID), treatment options, are discussed.

Language: Английский

Citations

6
SARS-CoV-2 Omicron BA.1 Variant Infection of Human Colon Epithelial Cells DOI Creative Commons
Avan Antia, David M. Alvarado, Qiru Zeng

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(4), P. 634 - 634

Published: April 19, 2024

The Omicron variant of SARS-CoV-2, characterized by multiple subvariants including BA.1, XBB.1.5, EG.5, and JN.1, became the predominant strain in early 2022. Studies indicate that replicates less efficiently lung tissue compared to ancestral strain. However, infectivity gastrointestinal tract is not fully defined, despite fact 70% COVID-19 patients experience digestive disease symptoms. Here, using primary human colonoids, we found that, regardless individual variability, infects colon cells similarly or effectively than Delta variant. induced limited type III interferon expression showed no significant impact on epithelial integrity. Further experiments revealed inefficient cell-to-cell spread spike protein cleavage protein, possibly contributing its lower infectious particle levels. findings highlight variant-specific replication differences providing insights into enteric tropism relevance long COVID

Language: Английский

Citations

5
Long COVID—ACOEM Guidance Statement DOI Open Access
Gregg M. Stave, Ismail Nabeel, Quentin Durand‐Moreau

et al.

Journal of Occupational and Environmental Medicine, Journal Year: 2024, Volume and Issue: 66(4), P. 349 - 357

Published: Feb. 2, 2024

Abstract Persistent symptoms are common after acute COVID-19, often referred to as long COVID. Long COVID may affect the ability perform activities of daily living, including work. occurs more frequently in those with severe COVID-19. This guidance statement reviews pathophysiology COVID-19 and provides pragmatic approaches symptoms, syndromes, conditions occupational setting. Disability laws workers’ compensation also addressed.

Language: Английский

Citations

4
Integrins as Therapeutic Targets for SARS-CoV-2 DOI Creative Commons
Timothy E. Gressett, Danielle Nader, Juan Pablo Robles

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: April 29, 2022

OPINION article Front. Cell. Infect. Microbiol., 29 April 2022Sec. Virus and Host https://doi.org/10.3389/fcimb.2022.892323

Language: Английский

Citations

19