scholarly journals DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

2021 ◽  
Vol 17 (5) ◽  
pp. e1009576
Author(s):  
Michel Thépaut ◽  
Joanna Luczkowiak ◽  
Corinne Vivès ◽  
Nuria Labiod ◽  
Isabelle Bally ◽  
...  
Keyword(s):  
Cell Infection ◽  
Lectin Receptors ◽  
Viral Dissemination ◽  
Sign Recognition ◽  
Virus Transfer ◽  
Molecular Events ◽  
Trans Infection ◽  
Direct Cell ◽  
Multiple Interaction ◽  
Antigen Presenting

The efficient spread of SARS-CoV-2 resulted in a unique pandemic in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in respiratory mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ Vero E6 cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. These data have been then confirmed using authentic SARS-CoV-2 virus and human respiratory cell lines. Thus, we described a mechanism potentiating viral spreading of infection.

scholarly journals DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

2020 ◽  
Author(s):  
Michel Thépaut ◽  
Joanna Luczkowiak ◽  
Corinne Vivès ◽  
Nuria Labiod ◽  
Isabelle Bally ◽  
...  
Keyword(s):  
Innate Immune ◽  
Cell Infection ◽  
Lectin Receptors ◽  
Sign Recognition ◽  
Virus Transfer ◽  
Molecular Events ◽  
Trans Infection ◽  
Direct Cell ◽  
Multiple Interaction ◽  
Antigen Presenting

SummaryThe efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in air mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. Thus, we described a mechanism potentiating viral capture and spreading of infection. Early involvement of APCs opens new avenues for understanding and treating the imbalanced innate immune response observed in COVID-19 pathogenesis

scholarly journals HIV-1 trans-Infection Mediated by DCs: The Tip of the Iceberg of Cell-to-Cell Viral Transmission

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 39
Author(s):  
Daniel Perez-Zsolt ◽  
Dàlia Raïch-Regué ◽  
Jordana Muñoz-Basagoiti ◽  
Carmen Aguilar-Gurrieri ◽  
Bonaventura Clotet ◽  
...  
Keyword(s):  
Immune Responses ◽  
Ebola Virus ◽  
Viral Transmission ◽  
Productive Infection ◽  
Lectin Receptors ◽  
Enveloped Viruses ◽  
Cellular Targets ◽  
Trans Infection ◽  
Antigen Presenting ◽  
Hiv 1

HIV-1 cell-to-cell transmission is key for an effective viral replication that evades immunity. This highly infectious mechanism is orchestrated by different cellular targets that utilize a wide variety of processes to efficiently transfer HIV-1 particles. Dendritic cells (DCs) are the most potent antigen presenting cells that initiate antiviral immune responses, but are also the cells with highest capacity to transfer HIV-1. This mechanism, known as trans-infection, relies on the capacity of DCs to capture HIV-1 particles via lectin receptors such as the sialic acid-binding I-type lectin Siglec-1/CD169. The discovery of the molecular interaction of Siglec-1 with sialylated lipids exposed on HIV-1 membranes has enlightened how this receptor can bind to several enveloped viruses. The outcome of these interactions can either mount effective immune responses, boost the productive infection of DCs and favour innate sensing, or fuel viral transmission via trans-infection. Here we review these scenarios focusing on HIV-1 and other enveloped viruses such as Ebola virus or SARS-CoV-2.

scholarly journals MGL Receptor and Immunity: When the Ligand Can Make the Difference

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ilaria Grazia Zizzari ◽  
Chiara Napoletano ◽  
Federico Battisti ◽  
Hassan Rahimi ◽  
Salvatore Caponnetto ◽  
...  
Keyword(s):  
Immune Response ◽  
Steric Structure ◽  
Activated Macrophages ◽  
Danger Signal ◽  
Lectin Receptors ◽  
Type C ◽  
The Difference ◽  
Antigen Presenting ◽  
Antigen Structure

C-type lectin receptors (CLRs) on antigen-presenting cells (APCs) facilitate uptake of carbohydrate antigens for antigen presentation, modulating the immune response in infection, homeostasis, autoimmunity, allergy, and cancer. In this review, we focus on the role of the macrophage galactose type C-type lectin (MGL) in the immune response against self-antigens, pathogens, and tumor associated antigens (TAA). MGL is a CLR exclusively expressed by dendritic cells (DCs) and activated macrophages (MØs), able to recognize terminal GalNAc residues, including the sialylated and nonsialylated Tn antigens. We discuss the effects on DC function induced throughout the engagement of MGL, highlighting the importance of the antigen structure in the modulation of immune response. Indeed modifying Tn-density, the length, and steric structure of the Tn-antigens can result in generating immunogens that can efficiently bind to MGL, strongly activate DCs, mimic the effects of a danger signal, and achieve an efficient presentation in HLA classes I and II compartments.

scholarly journals Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Guoping Zheng ◽  
Menghua Ge ◽  
Guanguan Qiu ◽  
Qiang Shu ◽  
Jianguo Xu
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Spinal Cord Injuries ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Cell Contact ◽  
Direct Cell ◽  
Almost All ◽  
Preclinical And Clinical Studies ◽  
Antigen Presenting

Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor-αstimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response. Because of their capacity for differentiation and immunomodulation, MSCs have been used in many preclinical and clinical studies as possible new therapeutic agents for the treatment of autoimmune, degenerative, and inflammatory diseases. In this review, we discuss the central role of MSCs in macrophage polarization and outcomes of diseases such as wound healing, brain/spinal cord injuries, and diseases of heart, lung, and kidney in animal models.

Molecular events in the processing of avidin by antigen-presenting cells (APC)

1983 ◽  
Vol 18 (3) ◽  
pp. 277-290 ◽  
Author(s):  
Aharon Friedman ◽  
Rachel Zerubavelt ◽  
Carlos Gitler ◽  
Irun R. Cohent
Keyword(s):  
Antigen Presenting Cells ◽  
Molecular Events ◽  
Antigen Presenting

scholarly journals Glycan Epitopes and Potential Glycoside Antagonists of DC-SIGN Involved in COVID-19: In Silico Study

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1586
Author(s):  
Meina Gao ◽  
Hui Li ◽  
Chenghao Ye ◽  
Kaixian Chen ◽  
Hualiang Jiang ◽  
...  
Keyword(s):  
In Silico ◽  
Systemic Infection ◽  
Intercellular Adhesion Molecule ◽  
Post Translational Modification ◽  
Sign Recognition ◽  
In Silico Study ◽  
Core Site ◽  
Dynamics Simulations ◽  
Antigen Presenting ◽  
Saikosaponin A

Glycosylation is an important post-translational modification that affects a wide variety of physiological functions. DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) is a protein expressed in antigen-presenting cells that recognizes a variety of glycan epitopes. Until now, the binding of DC-SIGN to SARS-CoV-2 Spike glycoprotein has been reported in various articles and is regarded to be a factor in systemic infection and cytokine storm. The mechanism of DC-SIGN recognition offers an alternative method for discovering new medication for COVID-19 treatment. Here, we discovered three potential pockets that hold different glycan epitopes by performing molecular dynamics simulations of previously reported oligosaccharides. The “EPN” motif, “NDD” motif, and Glu354 form the most critical pocket, which is known as the Core site. We proposed that the type of glycan epitopes, rather than the precise amino acid sequence, determines the recognition. Furthermore, we deduced that oligosaccharides could occupy an additional site, which adds to their higher affinity than monosaccharides. Based on our findings and previously described glycoforms on the SARS-CoV-2 Spike, we predicted the potential glycan epitopes for DC-SIGN. It suggested that glycan epitopes could be recognized at multiple sites, not just Asn234, Asn149 and Asn343. Subsequently, we found that Saikosaponin A and Liquiritin, two plant glycosides, were promising DC-SIGN antagonists in silico.

scholarly journals Hepatitis C Virus Modelling In Vitro and In Vivo

2021 ◽  
Author(s):  
Kenneth Blahut
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Infected Cell ◽  
Antiviral Therapy ◽  
Critical Role ◽  
Free Virus ◽  
Cell Infection ◽  
Local Modes ◽  
Direct Cell

Experiments have shown that hepatitis C virus (HCV) infections in vitro disseminate both distally via the release and diffusion of cell-free virus through the medium, and locally via direct, cell-to-cell transmission. To determine the relative contribution of each mode of infection to HCV dissemination, we developed an agent-based model (ABM) that explicitly incorporates both distal and local modes of infection. The ABM tracks the concentration of extracellular infectious virus in the supernatant and the number of intracellular HCV RNA segments within each infected cell over the course of simulated in vitro HCV infections. By constraining our ABM parameters using experimental data, we found that direct, cell-to-cell infection accounts for 98% (85%–100%, 95% credible region) of infection events, making it the dominant mode of HCV dissemination in vitro. Yet, while HCV spread via cell-free virus contributes little to the total number of infection events in vitro, it plays a critical role in enhancing cell-to-cell HCV dissemination by providing access to distant, uninfected areas, away from the already established large infection foci. Mathematical modelling of HCV load decay under antiviral therapy has allowed for the determination of antiviral efficacy and other important parameters. Current mathematical models (MMs) of HCV infection are based on a set of ordinary differential equations (ODEs) and assume that infectious cell lifespans are exponentially distributed over time, meaning that every infected cell has an equal probability of dying at any time. Here, we introduce a new MM which: (1) allows for a realistic eclipse delay between the moment of cell infection and the release of new virus; and (2) considers both exponential and (log)normal distributed durations for infectious cell lifespan, wherein cells are assumed to continuously producing virus. Application of this MM to HCV load data for patients undergoing antiviral therapy leads to different conclusions when predicting parameter values.

Highly glycosylated tumour antigens: interactions with the immune system

2011 ◽  
Vol 39 (1) ◽  
pp. 388-392 ◽  
Author(s):  
Eirikur Saeland ◽  
Yvette van Kooyk
Keyword(s):  
Immune System ◽  
Immune Modulation ◽  
Diagnostic Tools ◽  
Phenotypic Change ◽  
Carbohydrate Binding ◽  
Lectin Receptors ◽  
Functional Studies ◽  
Tumour Antigens ◽  
Antigen Presenting

A common phenotypic change in cancer is a dramatic transformation of cellular glycosylation. Functional studies of particular tumour-associated oligosaccharides are difficult to interpret conclusively, but carbohydrate-binding proteins are likely to contribute to progression of the tumour. This review discusses the potential role of CLRs (C-type lectin receptors), expressed by antigen-presenting cells of the immune system, in tumour recognition and immune modulation. Studies in recent years have provided significant insight into the immunomodulatory function of CLR during infections, but their role in cancer remains elusive; some strongly bind tumour cells and antigens, indicating participation in malignancy. The potential to use recombinant CLR as diagnostic tools will also be discussed.

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