ArticlePloS one2013
Role of the spike glycoprotein of human Middle East respiratory syndrome coronavirus (MERS-CoV) in virus entry and syncytia formation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 2 of them syntheses that pooled it.
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Who cites it
156 citing papers in PubMed, 2 syntheses or guidelines pooled it, 244 citations in OpenAlex.
- The Spike of SARS-CoV-2: Uniqueness and Applications.Frontiers in immunology · 2021Pooled it
- What Have We Learned About Middle East Respiratory Syndrome Coronavirus Emergence in Humans? A Systematic Literature Review.Vector borne and zoonotic diseases (Larchmont, N.Y.) · 2019Pooled it
- Q1020R in the spike proteins of MERS-CoV from Arabian camels confers resistance against soluble human DPP4.Journal of virology · 2026Article
- Clade C MERS-CoV camel strains vary in protease utilization during viral entry.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Characterisation of Naturally Occurring MERS-CoV Spike Mutations and Their Impact on Fusion and Neutralisation.Viruses · 2026Article
- A stabilized MERS-CoV spike ferritin nanoparticle vaccine elicits robust and protective neutralizing antibody responses.Nature communications · 2026Article
- Mathematical Modeling of Cell-Cell Fusion Assays to Characterize Virus-Mediated Cell Fusion.Advances in experimental medicine and biology · 2026Review
- Clade C MERS-CoV camel strains vary in protease utilization during viral entry.bioRxiv : the preprint server for biology · 2025Article
- Nasal mucus-derived KLK13 restricts SARS-CoV-2 infection via proteolytic cleavage of spike.mBio · 2025Article
- Syncytium: the viral escape room secret to persistent infection of SARS-CoV-2.Frontiers in microbiology · 2025Article
- Identification of the critical residues of TMPRSS2 for entry and host range of human coronavirus HKU1.Journal of virology · 2024Article
- Structure defining of ultrapotent neutralizing nanobodies against MERS-CoV with novel epitopes on receptor binding domain.PLoS pathogens · 2024Article
- AnHeliyon · 2024Article
- A Comparative Analysis of Molecular Biological Methods for the Detection of SARS-CoV-2 and Testing the In Vitro Infectivity of the Virus.Microorganisms · 2024Article
- Structural proteins of human coronaviruses: what makes them different?Frontiers in cellular and infection microbiology · 2024Review
- Mathematical Modeling of Virus-Mediated Syncytia Formation: Past Successes and Future Directions.Results and problems in cell differentiation · 2024Review
- Porcine deltacoronavirus resists antibody neutralization through cell-to-cell transmission.Emerging microbes & infections · 2023Article
- Ultrastructural study confirms the formation of single and heterotypic syncytial cells in bronchoalveolar fluids of COVID-19 patients.Virology journal · 2023Article
- MICaFVi: A Novel Magnetic Immuno-Capture Flow Virometry Nano-Based Diagnostic Tool for Detection of Coronaviruses.Biosensors · 2023Article
- Interspecies transmission of SARS CoV-2 with special emphasis on viral mutations and ACE-2 receptor homology roles.International journal of veterinary science and medicine · 2023Review
96 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
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 Eptesicus fuscus 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 NH4Cl 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.