Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia Formation
Identifieur interne : 001F15 ( Main/Exploration ); précédent : 001F14; suivant : 001F16Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia Formation
Auteurs : Zhaohui Qian [États-Unis, République populaire de Chine] ; Samuel R. Dominguez [États-Unis] ; Kathryn V. Holmes [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Descripteurs français
- KwdFr :
- Animaux, Cellules HEK293, Cellules Vero, Cellules géantes (virologie), Concentration en ions d'hydrogène, Coronavirus (physiologie), Délétion de gène, Endosomes (métabolisme), Expression des gènes, Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (métabolisme), Humains, Lentivirus (génétique), Lentivirus (métabolisme), Lignée cellulaire, Membrane cellulaire (métabolisme), Membrane cellulaire (virologie), Ordre des gènes, Pénétration virale, Récepteurs viraux (métabolisme), Souris, Tropisme viral, Trypsine (métabolisme).
- MESH :
- génétique : Glycoprotéine de spicule des coronavirus, Lentivirus.
- métabolisme : Endosomes, Glycoprotéine de spicule des coronavirus, Lentivirus, Membrane cellulaire, Récepteurs viraux, Trypsine.
- physiologie : Coronavirus.
- virologie : Cellules géantes, Membrane cellulaire.
- Animaux, Cellules HEK293, Cellules Vero, Concentration en ions d'hydrogène, Délétion de gène, Expression des gènes, Humains, Lignée cellulaire, Ordre des gènes, Pénétration virale, Souris, Tropisme viral.
English descriptors
- KwdEn :
- Animals, Cell Line, Cell Membrane (metabolism), Cell Membrane (virology), Chlorocebus aethiops, Coronavirus (physiology), Endosomes (metabolism), Gene Deletion, Gene Expression, Gene Order, Giant Cells (virology), HEK293 Cells, Humans, Hydrogen-Ion Concentration, Lentivirus (genetics), Lentivirus (metabolism), Mice, Receptors, Virus (metabolism), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (metabolism), Trypsin (metabolism), Vero Cells, Viral Tropism, Virus Internalization.
- MESH :
- chemical , genetics : Spike Glycoprotein, Coronavirus.
- chemical , metabolism : Receptors, Virus, Spike Glycoprotein, Coronavirus, Trypsin.
- genetics : Lentivirus.
- metabolism : Cell Membrane, Endosomes, Lentivirus.
- physiology : Coronavirus.
- virology : Cell Membrane, Giant Cells.
- Animals, Cell Line, Chlorocebus aethiops, Gene Deletion, Gene Expression, Gene Order, HEK293 Cells, Humans, Hydrogen-Ion Concentration, Mice, Vero Cells, Viral Tropism, Virus Internalization.
Abstract
Little is known about the biology of the emerging human group c betacoronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Because coronavirus spike glycoproteins (S) mediate virus entry, affect viral host range, and elicit neutralizing antibodies, analyzing the functions of MERS-CoV S protein is a high research priority. MERS-CoV S on lentivirus pseudovirions mediated entry into a variety of cell types including embryo cells from New World
Url:
DOI: 10.1371/journal.pone.0076469
PubMed: 24098509
PubMed Central: 3789674
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>Little is known about the biology of the emerging human group c betacoronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Because coronavirus spike glycoproteins (S) mediate virus entry, affect viral host range, and elicit neutralizing antibodies, analyzing the functions of MERS-CoV S protein is a high research priority. MERS-CoV S on lentivirus pseudovirions mediated entry into a variety of cell types including embryo cells from New World <italic>Eptesicus fuscus</italic>
bats. Surprisingly, a polyclonal antibody to the S protein of MHV, a group a murine betacoronavirus, cross-reacted in immunoblots with the S2 domain of group c MERS-CoV spike protein. MERS pseudovirions released from 293T cells contained only uncleaved S, and pseudovirus entry was blocked by lysosomotropic reagents NH<sub>4</sub>
Cl and bafilomycin and inhibitors of cathepsin L. However, when MERS pseudovirions with uncleaved S protein were adsorbed at 4°C to Vero E6 cells, brief trypsin treatment at neutral pH triggered virus entry at the plasma membrane and syncytia formation. When 293T cells producing MERS pseudotypes co-expressed serine proteases TMPRSS-2 or -4, large syncytia formed at neutral pH, and the pseudovirions produced were non-infectious and deficient in S protein. These experiments show that if S protein on MERS pseudovirions is uncleaved, then viruses enter by endocytosis in a cathepsin L-dependent manner, but if MERS-CoV S is cleaved, either during virus maturation by serine proteases or on pseudovirions by trypsin in extracellular fluids, then viruses enter at the plasma membrane at neutral pH and cause massive syncytia formation even in cells that express little or no MERS-CoV receptor. Thus, whether MERS-CoV enters cells within endosomes or at the plasma membrane depends upon the host cell type and tissue, and is determined by the location of host proteases that cleave the viral spike glycoprotein and activate membrane fusion.</p>
</div>
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<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
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<region><li>Colorado</li>
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<settlement><li>Pékin</li>
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