SARS-CoV-2 suppresses TLR4-induced immunity by dendritic cells via C-type lectin receptor DC-SIGN DOI Creative Commons
Lieve E. H. van der Donk, Marta Bermejo‐Jambrina, John L. van Hamme

и другие.

PLoS Pathogens, Год журнала: 2023, Номер 19(10), С. e1011735 - e1011735

Опубликована: Окт. 16, 2023

SARS-CoV-2 causes COVID-19, an infectious disease with symptoms ranging from a mild cold to severe pneumonia, inflammation, and even death. Although strong inflammatory responses are major factor in causing morbidity mortality, superinfections bacteria during COVID-19 often cause bacteremia sepsis. Aberrant immune might underlie increased sensitivity but the mechanisms remain unclear. Here we investigated whether directly suppresses bacteria. We studied functionality of human dendritic cells (DCs) towards variety bacterial triggers after exposure Spike (S) protein primary isolate (hCoV-19/Italy). Notably, pre-exposure DCs either S or led reduced type I interferon (IFN) cytokine response Toll-like receptor (TLR)4 agonist lipopolysaccharide (LPS), whereas other TLR agonists were not affected. interacted C-type lectin DC-SIGN and, notably, blocking antibodies restored IFN LPS. Moreover, kinase Raf-1 by small molecule inhibitor These results suggest that modulates DC function upon TLR4 triggering via DC-SIGN-induced pathway. data imply actively DC-SIGN, which account for higher mortality rates observed patients superinfections.

Язык: Английский

Syndecan-1 in liver pathophysiology DOI
Andrea Reszegi, Péter Tátrai, Eszter Regős

и другие.

AJP Cell Physiology, Год журнала: 2022, Номер 323(2), С. C289 - C294

Опубликована: Июнь 15, 2022

Syndecan-1 (SDC-1) is a heparan sulfate (HS)/chondroitin proteoglycan (PG) of the cell surface and extracellular matrix (ECM), which regulates broad spectrum physiological pathological processes such as proliferation, migration, inflammation, remodeling, wound healing, tumorigenesis. represents major PG liver, expressed by hepatocytes cholangiocytes, its elevated expression characteristic feature liver diseases. The highest syndecan-1 found in cirrhosis hepatocellular carcinoma (HCC) developed cirrhotic livers. In addition, being hepatitis C receptor, virus (HCV)-infected livers produce extremely large amounts syndecan-1. serum levels cleaved (shedded) domain have clinical significance, their increased concentration reflects on poor prognosis well cancer. vivo experiments confirmed that protects against early stages fibrogenesis mainly enhanced clearance transforming growth factor β1 (TGFβ1) thrombospondin-1 (THBS1) via circulation, hepatocarcinogenesis interfering with several signaling pathways enhancing cycle blockade. capable to hinder lipid metabolism ribosomal biogenesis induced cancer models. These observations together participation uptake viruses (e.g., HCV SARS-CoV-2) indicate central player pathologies.

Язык: Английский

Процитировано

20
Variant-specific interactions at the plasma membrane: Heparan sulfate’s impact on SARS-CoV-2 binding kinetics DOI Creative Commons
Dario Valter Conca, Fouzia Bano,

Julius von Wirén

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 10, 2024

Abstract The worldwide spread of SARS-CoV-2 has been characterised by the emergence several variants concern (VOCs) presenting an increasing number mutations in viral genome. spike glycoprotein, responsible for engaging receptor ACE2, exhibits highest density mutations, suggesting ongoing evolution to optimize entry. However, previous studies focussed on isolated molecular interactions, neglecting intricate composition plasma membrane and interplay between attachment factors. Our study explores role avidity complexity modulating virus-host binding kinetics during early stages entry original Wuhan strain three VOCs: Omicron BA.1, Delta, Alpha. We employ fluorescent liposomes decorated with from VOCs as virion mimics single-particle tracking native supported lipid bilayers derived pulmonary Calu-3 cells. findings reveal increase affinity multivalent bond cell surface driven increased association rate. show that heparan sulfate (HS), a sulfated glycosaminoglycan commonly expressed cells’ membrane, plays central interaction we observe shift its screening ACE2 important factor Omicron. This is caused ∼10-fold Omicron’s HS compared strain, shown using atomic force microscopy-based single-molecule spectroscopy. results importance coreceptors, particularly HS, modulation VOCs. highlight transition variants’ strategy towards use initial docking site, which likely shaping tropism infection upper airways, milder symptoms, higher transmissibility.

Язык: Английский

Процитировано

5
Heparan Sulfate and Sialic Acid in Viral Attachment: Two Sides of the Same Coin? DOI Open Access
Iván Ramos-Martínez, Edgar Ramos-Martínez, René Segura‐Velázquez

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(17), С. 9842 - 9842

Опубликована: Авг. 30, 2022

Sialic acids and heparan sulfates make up the outermost part of cell membrane extracellular matrix. Both structures are characterized by being negatively charged, serving as receptors for various pathogens, highly expressed in respiratory digestive tracts. Numerous viruses use to infect cells; this group HSV, HPV, SARS-CoV-2. Other require express sialic acids, is case influenza A adenoviruses. This review aims present, a general way, participation glycoconjugates viral entry, therapeutic strategies focused on inhibiting interaction between virus glycoconjugates. Interestingly, there few studies that suggest both addressed here. Considering biological redundancy exists we propose it important jointly evaluate design contemplate interactions approach will allow identifying new lead deeper understanding interspecies transmission.

Язык: Английский

Процитировано

17
Berbamine suppresses intestinal SARS-CoV-2 infection via a BNIP3-dependent autophagy blockade DOI Creative Commons
Alexandra P. M. Cloherty, Anusca G. Rader,

Kharishma S. Patel

и другие.

Emerging Microbes & Infections, Год журнала: 2023, Номер 12(1)

Опубликована: Март 23, 2023

SARS-CoV-2, the causative virus of COVID-19, continues to threaten global public health. COVID-19 is a multi-organ disease, causing not only respiratory distress, but also extrapulmonary manifestations, including gastrointestinal symptoms with SARS-CoV-2 RNA shedding in stool long after clearance. Despite vaccination and existing antiviral treatments, variants concern are still emerging circulating. Of note, new Omicron BA.5 sublineages both increasingly evade neutralizing antibodies demonstrate an increased preference for entry via endocytic route. Alternative direct-acting antivirals, host-directed therapies interfere host mechanisms hijacked by viruses, enhance cell-mediated resistance reduced likelihood drug development. Here, we that autophagy-blocking therapeutic berbamine dihydrochloride robustly prevents acquisition human intestinal epithelial cells autophagy-mediated BNIP3 mechanism. Strikingly, exhibited pan-antiviral activity against subvariants BA.2 at nanomolar potency, providing proof concept potential targeting autophagy machinery thwart infection current circulating subvariants. Furthermore, show limited virus-induced damage barrier function, affirming relevance manipulation avert permeability associated acute post-COVID-19 syndrome. Our findings underscore exploits dissemination indicate repurposed autophagy-based antivirals represent pertinent option boost protection ameliorate disease pathogenesis future concern.

Язык: Английский

Процитировано

11
SARS-CoV-2 suppresses TLR4-induced immunity by dendritic cells via C-type lectin receptor DC-SIGN DOI Creative Commons
Lieve E. H. van der Donk, Marta Bermejo‐Jambrina, John L. van Hamme

и другие.

PLoS Pathogens, Год журнала: 2023, Номер 19(10), С. e1011735 - e1011735

Опубликована: Окт. 16, 2023

SARS-CoV-2 causes COVID-19, an infectious disease with symptoms ranging from a mild cold to severe pneumonia, inflammation, and even death. Although strong inflammatory responses are major factor in causing morbidity mortality, superinfections bacteria during COVID-19 often cause bacteremia sepsis. Aberrant immune might underlie increased sensitivity but the mechanisms remain unclear. Here we investigated whether directly suppresses bacteria. We studied functionality of human dendritic cells (DCs) towards variety bacterial triggers after exposure Spike (S) protein primary isolate (hCoV-19/Italy). Notably, pre-exposure DCs either S or led reduced type I interferon (IFN) cytokine response Toll-like receptor (TLR)4 agonist lipopolysaccharide (LPS), whereas other TLR agonists were not affected. interacted C-type lectin DC-SIGN and, notably, blocking antibodies restored IFN LPS. Moreover, kinase Raf-1 by small molecule inhibitor These results suggest that modulates DC function upon TLR4 triggering via DC-SIGN-induced pathway. data imply actively DC-SIGN, which account for higher mortality rates observed patients superinfections.

Язык: Английский

Процитировано

11