ArticlePLoS pathogens2017
The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
108 citing papers in PubMed, 154 citations in OpenAlex.
- Repurposing screens reveal a role for PKCη and NF1 in SARS-CoV-2 infection.PLoS pathogens · 2026Article
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- Conserved use of tetraspanin CD9 as an entry receptor by rhabdoviruses spanning multiple genera.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Proteomic Analysis of COVID-19 Infection.Advances in experimental medicine and biology · 2026Article
- Article
- Review
- Review
- Porcine hemagglutinating encephalomyelitis virus VW572 (not Gent/PS412 and Labadie) uses the CD81 receptor and MVB-derived exosomal pathway for efficient entry and spread in neuronal cells.Journal of virology · 2025Article
- Lipids, Tetraspanins, and Exosomes: Cell Factors inViruses · 2025Review
- Article
- Distinctive Features of Extracellular Vesicles Present in the Gastric Juice of Patients with Gastric Cancer and Healthy Subjects.International journal of molecular sciences · 2025Article
- ACE2 from Pipistrellus abramus bats is a receptor for HKU5 coronaviruses.Nature communications · 2025Article
- Single-cell transcriptomics of bronchoalveolar lavage during PRRSV infection with different virulence.Nature communications · 2025Article
- Oncolytic alphavirus-induced extracellular vesicles counteract the immunosuppressive effect of melanoma-derived extracellular vesicles.Scientific reports · 2025Article
- Middle East respiratory syndrome coronavirus (MERS-CoV) internalization does not rely on DPP4 cytoplasmic tail signaling.Npj viruses · 2024Article
- Extracellular vesicles containing SARS-CoV-2 proteins are associated with multi-organ dysfunction and worse outcomes in patients with severe COVID-19.Journal of extracellular vesicles · 2024Article
- Article
- Mapping immunodominant sites on the MERS-CoV spike glycoprotein targeted by infection-elicited antibodies in humans.Cell reports · 2024Article
- Tetraspanin proteins in membrane remodeling processes.Journal of cell science · 2024Review
48 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease. This CD9-facilitated condensation of receptors and proteases allowed MERS-CoV pseudoviruses to enter cells rapidly and efficiently. Without CD9, MERS-CoV viruses were not activated by TTSPs, and they trafficked into endosomes to be cleaved much later and less efficiently by cathepsins. Thus, we identified DPP4:CD9:TTSP as the protein complexes necessary for early, efficient MERS-CoV entry. To evaluate the importance of these complexes in an in vivo CoV infection model, we used recombinant Adenovirus 5 (rAd5) vectors to express human DPP4 in mouse lungs, thereby sensitizing the animals to MERS-CoV infection. When the rAd5-hDPP4 vectors co-expressed small RNAs silencing Cd9 or Tmprss2, the animals were significantly less susceptible, indicating that CD9 and TMPRSS2 facilitated robust in vivo MERS-CoV infection of mouse lungs. Furthermore, the S proteins of virulent mouse-adapted MERS-CoVs acquired a CD9-dependent cell entry character, suggesting that CD9 is a selective agent in the evolution of CoV virulence.
Indexed as
Identifiers
What OpenQuestion holds
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.