ArticleProceedings of the National Academy of Sciences of the United States of America2016
Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 221 papers.
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221 citing papers in PubMed, 338 citations in OpenAlex.
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- 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
- Clade C MERS-CoV camel strains vary in protease utilization during viral entry.bioRxiv : the preprint server for biology · 2025Article
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- Yeast-two-hybrid based high-throughput screening to discover SARS-CoV-2 fusion inhibitors by targeting the HR1/HR2 interaction.Acta pharmaceutica Sinica. B · 2025Article
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- Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses.Cell · 2025Article
- Characterization of spike S1/S2 processing and entry pathways of lentiviral pseudoviruses bearing seasonal human coronaviruses NL63, 229E, and HKU1 spikes.Microbiology spectrum · 2025Article
- ACE2 utilization of HKU25 clade MERS-related coronaviruses with broad geographic distribution.bioRxiv : the preprint server for biology · 2025Article
- Viral glycoprotein-mediated entry and antibody-mediated immunity in HIV-1 and SARS-CoV-2 infection.Frontiers in immunology · 2025Review
- Article
161 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans from zoonotic sources and causes severe pulmonary disease. Virions require spike (S) glycoproteins for binding to cell receptors and for catalyzing virus-cell membrane fusion. Fusion occurs only after S proteins are cleaved sequentially, first during their secretion through the exocytic organelles of virus-producing cells, and second after virus binding to target-cell receptors. To more precisely determine how sequential proteolysis contributes to CoV infection, we introduced S mutations obstructing the first cleavages. These mutations severely compromised MERS-CoV infection into human lung-derived cells, but had little effect on infection into several other cell types. These cell type-specific requirements for proteolysis correlated with S conformations during cell entry. Without the first cleavages, S proteins resisted cell receptor-induced conformational changes, which restricted the second, fusion-activating cleavages. Consistent with these findings, precleaved MERS viruses used receptor-proximal, cell-surface proteases to effect the second fusion-activating cleavages during cell entry, whereas the more rigid uncleaved MERS viruses trafficked past these cell-surface proteases and into endosomes. Uncleaved viruses were less infectious to human airway epithelial and Calu3 cell cultures because they lacked sufficient endosomal fusion-activating proteases. Thus, by sensitizing viruses to receptor-induced conformational changes, the first S cleavages expand virus tropism to cell types that are relevant to lung infection, and therefore may be significant determinants of MERS-CoV virulence.
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