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Literature detail

Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding.

Susanna K P Lau1,2,3,4 Libiao Zhang5 Hayes K H Luk2 Lifeng Xiong2 Xingwen Peng5 Kenneth S M Li2 Xiangyang He5 Pyrear Su-Hui Zhao2 Rachel Y Y Fan2 Antonio C P Wong2 Syed Shakeel Ahmed2 Jian-Piao Cai2 Jasper F W Chan1,2,3,4 Yinyan Sun6 Dongyan Jin7 Honglin Chen1,2,3,4 Terrence C K Lau8 Raven K H Kok1,2,3,4 Wenhui Li6 Kwok-Yung Yuen1,2,3,4 Patrick C Y Woo1,2,3,4
Affiliations 8 institutions
  1. State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong, China.
  2. Department of Microbiology The University of Hong Kong, China.
  3. Carol Yu Centre for Infection The University of Hong Kong, China.
  4. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China.
  5. Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, and Guangdong Institute of Applied Biological Resources, Guangzhou, Guangdong Province, China.
  6. National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, Beijing, China.
  7. School of Biomedical Sciences, The University of Hong Kong, China.
  8. Department of Biomedical Sciences, City University of Hong Kong, China.
PMID 29346682 2018 J Infect Dis eng ppublish
PubMed DOI Browse context

Article

Publication summary

Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4.

Chiroptera Evolution, Molecular Virus Internalization Animals Betacoronavirus Dipeptidyl Peptidase 4 HEK293 Cells Humans Phylogeny Protein Binding Receptors, Virus Sequence Analysis, DNA Spike Glycoprotein, Coronavirus DPP4 protein, human

Structured evidence records

Evidence records

3 total
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.90
Key finding

Genomic and phylogenetic analysis placed the spike gene of Hp-BatCoV HKU25 in an intermediate position between HKU4 and HKU5, revealing stepwise molecular evolution among bat lineage C betacoronaviruses toward MERS-CoV.

Location
Not specified
Supporting text

We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5.

Genes or proteins
spike protein
Analysis methods
phylogenetic analysis; sequence analysis
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

The spike protein of Hp-BatCoV HKU25 from bats can bind and utilize the human receptor dipeptidyl peptidase 4 (hDPP4) for cell entry, indicating molecular adaptation toward human receptor usage.

Host
Not specified
Location
Not specified
Supporting text

The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike.

Genes or proteins
spike; RBD
Receptors
hDPP4
Mechanism types
receptor_binding; cell_entry
Receptor Usage 1 records
Receptor Usage Extraction confidence 1.00
Key finding

Hp-BatCoV HKU25 spike binds human dipeptidyl peptidase 4 (hDPP4) and mediates receptor-dependent cell entry with lower efficiency than MERS-CoV spike.

Location
Not specified
Supporting text

The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells.

Method
binding assay; pseudovirus assay
Receptors
hDPP4