ArticleProceedings of the National Academy of Sciences of the United States of America2014
Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers, 1 of them a synthesis that pooled it.
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
211 citing papers in PubMed, 1 synthesis or guideline pooled it, 296 citations in OpenAlex.
- 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
- Aminopeptidase N is a receptor for hedgehog merbecoviruses.Nature microbiology · 2026Article
- Addressing the zoonotic threat of merbecoviruses.Nature microbiology · 2026Review
- Exploring coronavirus cell entry with functional viromics.Journal of virology · 2026Review
- Immunogenicity and protective efficacy of MERS CoV, NL140422, and HKU4 spike protein nanoparticle vaccines.Npj viruses · 2026Article
- Development and Application of a Pseudovirus-Based Assay for Modelling SARS-CoV-2 Spike Protein Mediated Drug Screening.International journal of molecular sciences · 2026Article
- Structural basis for human DPP4 receptor recognition by MERS-like coronaviruses 2014-422 and GX2012.PLoS pathogens · 2026Article
- From zoonotic spillover to endemicity: the broad determinants of human coronavirus tropism.mBio · 2025Review
- HKU25 clade MERS-related coronaviruses use ACE2 as a functional receptor.Nature microbiology · 2025Article
- Structural and phenotypic plasticity of the RBD loop2 region is a key determinant for HKU5r-CoVs' emergence in mink.bioRxiv : the preprint server for biology · 2025Article
- Bat sarbecovirus WIV1-CoV bears an adaptive mutation that alters spike dynamics and enhances ACE2 binding.PLoS pathogens · 2025Article
- Structural and functional constraints on spike activation and host protease utilization limit cell entry of SARS-CoV-2-related bat coronaviruses.Journal of virology · 2025Article
- MERS-related coronavirus circulating in pangolins exhibits strong fusogenicity in human cells and high sensitivity to fusion inhibitors.Cell reports. Medicine · 2025Article
- Characterization of a MERS-related betacoronavirus in Danish brown long-eared bats (Plecotus auritus).Virology journal · 2025Article
- Exploring the Use of Viral Vectors Pseudotyped with Viral Glycoproteins as Tools to Study Antibody-Mediated Neutralizing Activity.Microorganisms · 2025Review
- Merbecovirus S2 subunit vaccines elicit cross reactive antibodies and provide partial protection against MERS coronavirus.Npj viruses · 2025Article
- HKU5 bat merbecoviruses engage bat and mink ACE2 as entry receptors.Nature communications · 2025Article
- Article
- Synergistic activation of bat SARS-like coronaviruses spike protein by elastase and TMPRSS2.Scientific reports · 2025Article
- Structures and receptor binding activities of merbecovirus spike proteins reveal key signatures for human DPP4 adaptation.Science advances · 2025Article
151 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
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes ∼ 36% fatality in infected patients. Believed to have originated from bats, MERS-CoV is genetically related to bat coronaviruses HKU4 and HKU5. To understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of HKU4 and HKU5. We found that dipeptidyl peptidase 4 (DPP4), the receptor for MERS-CoV, is also the receptor for HKU4, but not HKU5. Despite sharing a common receptor, MERS-CoV and HKU4 spikes demonstrated functional differences. First, whereas MERS-CoV prefers human DPP4 over bat DPP4 as its receptor, HKU4 shows the opposite trend. Second, in the absence of exogenous proteases, both MERS-CoV and HKU4 spikes mediate pseudovirus entry into bat cells, whereas only MERS-CoV spike, but not HKU4 spike, mediates pseudovirus entry into human cells. Thus, MERS-CoV, but not HKU4, has adapted to use human DPP4 and human cellular proteases for efficient human cell entry, contributing to the enhanced pathogenesis of MERS-CoV in humans. These results establish DPP4 as a functional receptor for HKU4 and host cellular proteases as a host range determinant for HKU4. They also suggest that DPP4-recognizing bat coronaviruses threaten human health because of their spikes' capability to adapt to human cells for cross-species transmissions.
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.