scholarly journals SARS-CoV-2 Spike Protein Dictates Syncytium-mediated Lymphocyte Elimination

2021 ◽  
Author(s):  
Qiang Sun ◽  
Zhengrong Zhang ◽  
You Zheng ◽  
Zubiao Niu ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Cell Formation ◽  
Surface Glycoprotein ◽  
Cellular Structures ◽  
Direct Result ◽  
Spike Glycoprotein ◽  
Cell Structures ◽  
Typical Cell ◽  
Glycoprotein Processing ◽  
Underlying Mechanisms

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (approximately 45.1 nm/sec) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.

Unique nCoV-2019 (COVID 19) spike glycoprotein processing by host protease: Analysis and Implication on infection

2020 ◽  
Vol 17 ◽  
Author(s):  
Ajoy Basak ◽  
Sarmistha Basak
Keyword(s):  
World Health ◽  
Spike Glycoprotein ◽  
Binding Domains ◽  
Corona Virus ◽  
Global Pandemic ◽  
High Infection ◽  
Crucial Information ◽  
Glycoprotein Processing ◽  
Health Organization ◽  
Host Reservoir

: The current global pandemic outbreak of a novel type of corona virus termed by World Health Organization as COVID-19 became an grave concern and worry to human health and world economy. Intense research efforts are now underway worldwide to combat and prevent the spread of this deadly disease. This zoonotic virus, a native to bat population is most likely transmitted to human via a host reservoir. Due to its close similarity to previously known SARS CoV (Severe Acute Respiratory Syndrome Corona Virus) of 2002 and related MERS CoV (Middle East Respiratory Syndrome Corona Virus) of 2012, it is also known as SARS CoV2. But unlike them it is far too infectious, virulent and lethal. Among its various proteins, the surface spike glycoprotein “S” has drawn significant attention because of its implication in viral recognition and host-virus fusion process. A detail comparative analysis of “S” proteins of SARS CoV (now called SARS CoV1), SARS CoV2 (COVID-19) and MERS CoV based on structure, sequence alignment, host cleavage sites, receptor binding domains, potential glycosylation and Cys-disulphide bridge locations has been performed. It revealed some key features and variations that may elucidate the high infection and virulence character of COVID-19. Moreover this crucial information may become useful in our quest for COVID-19 therapeutics and vaccines.

scholarly journals In situ structure and organization of the influenza C virus surface glycoprotein

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Steinar Halldorsson ◽  
Kasim Sader ◽  
Jack Turner ◽  
Lesley J. Calder ◽  
Peter B. Rosenthal
Keyword(s):  
Membrane Fusion ◽  
Hexagonal Lattice ◽  
Surface Glycoprotein ◽  
Structural Basis ◽  
Virus Surface ◽  
The Matrix ◽  
Influenza C Virus ◽  
Subtomogram Averaging ◽  
Electron Cryotomography

AbstractThe lipid-enveloped influenza C virus contains a single surface glycoprotein, the haemagglutinin-esterase-fusion (HEF) protein, that mediates receptor binding, receptor destruction, and membrane fusion at the low pH of the endosome. Here we apply electron cryotomography and subtomogram averaging to describe the structural basis for hexagonal lattice formation by HEF on the viral surface. The conformation of the glycoprotein in situ is distinct from the structure of the isolated trimeric ectodomain, showing that a splaying of the membrane distal domains is required to mediate contacts that form the lattice. The splaying of these domains is also coupled to changes in the structure of the stem region which is involved in membrane fusion, thereby linking HEF’s membrane fusion conformation with its assembly on the virus surface. The glycoprotein lattice can form independent of other virion components but we show a major role for the matrix layer in particle formation.

scholarly journals Viscoelastic Properties of Cell Structures Manufactured Using a Photo-Curable Additive Technology—PJM

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1895
Author(s):  
Tomasz Kozior ◽  
Czesław Kundera
Keyword(s):  
Viscoelastic Properties ◽  
Cellular Structure ◽  
Material Selection ◽  
Cellular Structures ◽  
Test Results ◽  
Additive Technology ◽  
Polymer Resin ◽  
Cell Structures ◽  
Relaxation Curves ◽  
The Impact

This research paper reviews the test results involving viscoelastic properties of cellular structure models made with the PolyJet Matrix—PJM additive technology. The designed test specimens were of complex cellular structure and made of three various photo-curable polymer resin types. Materials were selected taking into account the so-called “soft” and “tough” material groups. Compressive stress relaxation tests were conducted in accordance with the recommendations of standard ISO 3384, and the impact of the geometric structure shape and material selection on viscoelastic properties, as well as the most favorable geometric variants of the tested cellular structure models were determined. Mathematica and Origin software was used to conduct a statistical analysis of the test results and determine five-parameter functions approximating relaxation curves. The most favorable rheological was adopted and its mean parameters determined, which enables to match both printed model materials and their geometry in the future, to make a component with a specific rheological response. Furthermore, the test results indicated that there was a possibility of modelling cellular structures within the PJM technology, using support material as well.

Computational and Experimental Studies of Cellular Samples Manufactured Using Additive Methods for Use in Advanced Lightweight Designs of Engine Parts

2020 ◽  
Author(s):  
Liubov Magerramova ◽  
Michael Volkov ◽  
Oleg Volgin ◽  
Pavel Kolos
Keyword(s):  
Fatigue Testing ◽  
Low Cycle Fatigue ◽  
Cell Structure ◽  
Experimental Studies ◽  
Cellular Structures ◽  
Uniaxial Tensile ◽  
Porous Structures ◽  
Lattice Cell ◽  
Cell Structures ◽  
Homogeneous Materials

Abstract The use of cellular structures is one way to reduce the weight of engine parts. Cellular structures are used to provide rigidity and strength for parts subject to compression, bending, and shock loads. Failure of the individual elements of a lattice/cell structure does not result in the destruction of the entire part; this stands in contrast to the structure of a conventional homogeneous metal object, in which cracks will continue to increase with increasing load, causing the destruction of the entire part. Lattice/cell structures have relatively high characteristics of rigidity and strength, excellent thermal insulation properties, energy absorption characteristics, and high fatigue resistance. The use of this type of structure in engine part construction opens up new opportunities for advanced aviation applications. However, the deformation behavior of porous and metallic structures differs significantly from that of conventional homogeneous materials. Samples with cellular and porous structures are themselves designs. Therefore, procedures for strength testing and interpretation of experimental results for cellular and porous structures differ from those for samples derived from homogeneous materials. The criteria for determining the properties of cellular structures include density, stiffness, ability to accumulate energy, etc. These parameters depend on the configuration of the cells, the size of each cell, and the thickness of the connecting elements. Mechanical properties of cellular structures can be established experimentally and confirmed numerically. Special cellular specimens have been designed for uniaxial tensile, bending, compression, shear, and low-cycle fatigue testing. Several variants of cell structures with relative densities ranging from 13 to 45% were considered. Specifically, the present study examined the stress-strain states of cell structures from brands “CobaltChrome MP1” powder compositions obtained by laser synthesis on an industrial 3D printer Concept Laser M2 Cusing Single Laser 400W. Numerical simulations of the tests were carried out by the finite element method. Then, the most rational cellular structures in terms of mass and strength were established on the basis of both real and numerical experiments.

Computational and Experimental Studies of Cellular Samples Manufactured Using Additive Methods for Use in Advanced Lightweight Designs of Engine Parts

2020 ◽  
Author(s):  
Liubov Magerramova ◽  
Michael Volkov ◽  
Oleg Volgin ◽  
Pavel Kolos
Keyword(s):  
Fatigue Testing ◽  
Low Cycle Fatigue ◽  
Experimental Studies ◽  
Cellular Structures ◽  
Uniaxial Tensile ◽  
Porous Structures ◽  
Cell Structures ◽  
Engine Part ◽  
Homogeneous Materials ◽  
High Fatigue

Abstract Lattice/cell structures have relatively high characteristics of rigidity and strength, excellent thermal insulation properties, energy absorption characteristics, and high fatigue resistance. The use of this type of structure in engine part construction opens up new opportunities for advanced aviation applications. However, the deformation behavior of porous and metallic structures differs significantly from that of conventional homogeneous materials. Samples with cellular and porous structures are themselves designs. Therefore, procedures for strength testing and interpretation of experimental results for cellular and porous structures differ from those for samples derived from homogeneous materials. The criteria for determining the properties of cellular structures include density, stiffness, ability to accumulate energy, etc. These parameters depend on the configuration of the cells, the size of each cell, and the thickness of the connecting elements. Mechanical properties of cellular structures can be established experimentally and confirmed numerically. Special cellular specimens have been designed for uniaxial tensile, bending, compression, shear, and low-cycle fatigue testing. Several variants of cell structures with relative densities ranging from 13 to 45% were considered. Specifically, the present study examined the stress-strain states of cell structures from brands "CobaltChrome MP1" powder compositions obtained by laser synthesis on an industrial 3D printer Concept Laser M2 Cusing Single Laser 400W. Numerical simulations of the tests were carried out by the finite element method. Then, the most rational cellular structures in terms of mass and strength were established on the basis of both real and numerical experiments.

scholarly journals Optimized Pseudotyping Conditions for the SARS-COV-2 Spike Glycoprotein

2020 ◽  
Vol 94 (21) ◽  
Author(s):  
Marc C. Johnson ◽  
Terri D. Lyddon ◽  
Reinier Suarez ◽  
Braxton Salcedo ◽  
Mary LePique ◽  
...  
Keyword(s):  
Signal Peptide ◽  
Neutralizing Antibodies ◽  
Particle Production ◽  
Surface Glycoprotein ◽  
Spike Protein ◽  
Target Cells ◽  
Spike Glycoprotein ◽  
Infectious Particle ◽  
Pathogenic Virus ◽  
Hiv 1

ABSTRACT The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) Spike glycoprotein is solely responsible for binding to the host cell receptor and facilitating fusion between the viral and host membranes. The ability to generate viral particles pseudotyped with SARS-COV-2 Spike is useful for many types of studies, such as characterization of neutralizing antibodies or development of fusion-inhibiting small molecules. Here, we characterized the use of a codon-optimized SARS-COV-2 Spike glycoprotein for the generation of pseudotyped HIV-1, murine leukemia virus (MLV), and vesicular stomatitis virus (VSV) particles. The full-length Spike protein functioned inefficiently with all three systems but was enhanced over 10-fold by deleting the last 19 amino acids of the cytoplasmic tail. Infection of 293FT target cells was possible only if the cells were engineered to stably express the human angiotensin-converting enzyme 2 (ACE2) receptor, but stably introducing an additional copy of this receptor did not further enhance susceptibility. Stable introduction of the Spike-activating protease TMPRSS2 further enhanced susceptibility to infection by 5- to 10-fold. Replacement of the signal peptide of the Spike protein with an optimal signal peptide did not enhance or reduce infectious particle production. However, modifications D614G and R682Q further enhanced infectious particle production. With all enhancing elements combined, the titer of pseudotyped HIV-1 particles reached almost 106 infectious particles/ml. Finally, HIV-1 particles pseudotyped with SARS-COV-2 Spike were successfully used to detect neutralizing antibodies in plasma from coronavirus disease 2019 (COVID-19) patients, but not in plasma from uninfected individuals. IMPORTANCE In work with pathogenic viruses, it is useful to have rapid quantitative tests for viral infectivity that can be performed without strict biocontainment restrictions. A common way of accomplishing this is to generate viral pseudoparticles that contain the surface glycoprotein from the pathogenic virus incorporated into a replication-defective viral particle that contains a sensitive reporter system. These pseudoparticles enter cells using the glycoprotein from the pathogenic virus, leading to a readout for infection. Conditions that block entry of the pathogenic virus, such as neutralizing antibodies, will also block entry of the viral pseudoparticles. However, viral glycoproteins often are not readily suited for generating pseudoparticles. Here, we describe a series of modifications that result in the production of relatively high-titer SARS-COV-2 pseudoparticles that are suitable for the detection of neutralizing antibodies from COVID-19 patients.

scholarly journals The S2 subunit of the spike glycoprotein of bovine coronavirus mediates membrane fusion in insect cells

Virology ◽  
1991 ◽  
Vol 180 (1) ◽  
pp. 395-399 ◽  
Author(s):  
Dongwan Yoo ◽  
Michael D. Parker ◽  
Lorne A. Babiuk
Keyword(s):  
Membrane Fusion ◽  
Insect Cells ◽  
Spike Glycoprotein ◽  
Bovine Coronavirus

scholarly journals An Aromatic Side Chain Is Required at Residue 8 of SU for Fusion of Ecotropic Murine Leukemia Virus

2004 ◽  
Vol 78 (1) ◽  
pp. 508-512 ◽  
Author(s):  
Zhaohui Qian ◽  
Lorraine M. Albritton
Keyword(s):  
Membrane Fusion ◽  
Aromatic Ring ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Surface Glycoprotein ◽  
Side Chain ◽  
Complete Fusion ◽  
Aromatic Side Chain ◽  
Fusion Pores ◽  
Murine Leukemia

ABSTRACT The surface glycoprotein (SU) of most gammaretroviruses contains a conserved histidine at its amino terminus. In ecotropic murine leukemia virus SU, replacement of histidine 8 with arginine (H8R) or deletion of H8 (H8del) abolishes infection and cell-cell fusion but has no effect on binding to the cellular receptor. We report here that an aromatic ring side chain is essential to the function of residue 8. The size of the aromatic ring appears to be important, as does its ability to form a hydrogen bond. In addition, infection by all of the nonaromatic amino acid substitutions could be partially rescued by the addition of two suppressor mutations (glutamine 227 to arginine [Q227R] and aspartate 243 to tyrosine [D243Y]) or by exposure to chlorpromazine, an agent that induces fusion pores in hemifusion intermediates to complete fusion, suggesting that, like the previously described H8R mutant, the mutants reported here also arrest membrane fusion at the hemifusion state. We propose that H8 is a key switch-point residue in the conformation changes that lead to membrane fusion and present a possible mechanism for how its substitution arrests fusion at the hemifusion state.

scholarly journals COLLAPSE BEHAVIOR OF DYNAMICALLY CRASHED HEXAGONAL THIN WALLED STRUCTURES WITH MULTI-CELL CROSS-SECTION GEOMETRY

2017 ◽  
Vol 20 (2) ◽  
Author(s):  
VLAD ANDREI CIUBOTARIU
Keyword(s):  
Cross Section ◽  
Cell Formation ◽  
Thin Walled Structures ◽  
Cell Structures ◽  
Identical Cell ◽  
Interior Walls ◽  
Collapse Behavior ◽  
Shape Characteristics ◽  
The Impact ◽  
Cross Section Geometry

<p>In previous studies, the cross-section geometries were either single cell (circular, prismatic) or multi-cell structures with identical cell properties. In the present research the collapse characterization of multi-cell structures consisting of three different types of cell formation defined by either two wide or two narrow angles separating the ladders is conducted. The shape characteristics of interest sum up the layout of the interior walls and their constraints over the outer structure walls. To study the control of cross-section geometry over the crashing mechanism, local or global progressive buckling response, energy absorption and crash load for the structures in discussion FEA simulations of the impact were performed.</p>

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