Literature detail

Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26.

Qihui Wang¹ Jianxun Qi¹ Yuan Yuan^2,3 Yifang Xuan⁴ Pengcheng Han⁵ Yuhua Wan^2,6 Wei Ji⁷ Yan Li¹ Ying Wu¹ Jianwei Wang⁸ Aikichi Iwamoto^9,10 Patrick C Y Woo^11,12 Kwok-Yung Yuen^11,13,14 Jinghua Yan¹ Guangwen Lu¹ George F Gao^{2,15,16,17,18,19}

Affiliations 19 institutions

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui Province, China.
Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
School of Life Sciences, Anhui University, Hefei 230039, China.
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
China-Japan Joint Laboratory of Molecular Microbiology and Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
Division of Infectious Diseases, Advanced Clinical Research Center, Department of Infectious Diseases and Applied Immunology, Research Hospital, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China
Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China.
Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui Province, China
Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China
Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. Electronic address: [email protected].

PMID 25211075 2014 Cell Host Microbe eng ppublish

PubMed DOI Browse context

Article

Publication summary

The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) is phylogenetically closely related to the bat coronaviruses (BatCoVs) HKU4 and HKU5. However, the evolutionary pathway of MERS-CoV is still unclear. A receptor binding domain (RBD) in the MERS-CoV envelope-embedded spike protein specifically engages human CD26 (hCD26) to initiate viral entry. The high sequence identity in the viral spike protein prompted us to investigate if HKU4 and HKU5 can recognize hCD26 for cell entry. We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition. The structure of the HKU4-RBD/hCD26 complex revealed a hCD26-binding mode similar overall to that observed for MERS-RBD. HKU4-RBD, however, is less adapted to hCD26 than MERS-RBD, explaining its lower affinity for receptor binding. Our findings support a bat origin for MERS-CoV and indicate the need for surveillance of HKU4-related viruses in bats.

Amino Acid Sequence Animals Chiroptera Coronavirus Coronavirus Infections Dipeptidyl Peptidase 4 Humans Middle East Respiratory Syndrome Coronavirus Molecular Sequence Data Phylogeny Protein Binding Receptors, Virus Sequence Alignment Spike Glycoprotein, Coronavirus

Structured evidence records

Evidence records

7 total

Receptor Usage 3 records

Receptor Usage Extraction confidence 1.00

Key finding

Bat coronavirus HKU4 uses human CD26 (DPP4) as a receptor for cell entry, while HKU5 does not.

Virus

Host

Location

Supporting text

We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition.

Method: binding assay; pseudovirus assay; structural analysis
Receptors: human CD26

Receptor Usage Extraction confidence 1.00

Key finding

Bat coronavirus HKU5 does not bind to human CD26 and is unable to use it for cell entry.

Virus

Host

Location

Supporting text

We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition.

Method: binding assay
Receptors: human CD26

Receptor Usage Extraction confidence 1.00

Key finding

MERS-CoV spike protein binds human CD26 (DPP4) to initiate viral entry.

Virus

Host

Location

Supporting text

A receptor binding domain (RBD) in the MERS-CoV envelope-embedded spike protein specifically engages human CD26 (hCD26) to initiate viral entry.

Receptors: human CD26

Molecular Adaptation 2 records

Molecular Adaptation Extraction confidence 0.90

Key finding

The bat coronavirus HKU4 spike receptor-binding domain binds human CD26 for cell entry, demonstrating partial molecular adaptation similar to but less optimized than MERS-CoV.

Virus

Host

Location

Supporting text

We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition. The structure of the HKU4-RBD/hCD26 complex revealed a hCD26-binding mode similar overall to that observed for MERS-RBD. HKU4-RBD, however, is less adapted to hCD26 than MERS-RBD.

Genes or proteins: spike; RBD
Receptors: CD26
Mechanism types: receptor_binding; cell_entry; host_adaptation

Molecular Adaptation Extraction confidence 0.90

Key finding

MERS-CoV spike receptor-binding domain interacts specifically with human CD26 to mediate viral entry, defining a molecular adaptation supporting human infection.

Virus

Host

Location

Supporting text

A receptor binding domain (RBD) in the MERS-CoV envelope-embedded spike protein specifically engages human CD26 (hCD26) to initiate viral entry.

Genes or proteins: spike; RBD
Receptors: CD26
Mechanism types: receptor_binding; cell_entry; host_adaptation

Genomic Evolution 1 records

Genomic Evolution Extraction confidence 0.95

Key finding

Phylogenetic analysis shows MERS-CoV is closely related to bat coronaviruses HKU4 and HKU5, supporting its evolutionary origin from bats.

Virus

Host

Location

Supporting text

Genes or proteins: spike
Analysis methods: phylogenetic analysis; sequence identity comparison

Zoonotic Surveillance 1 records

Zoonotic Surveillance Extraction confidence 0.60

Key finding

The authors highlight the need for surveillance of HKU4-related viruses in bats to monitor potential zoonotic coronaviruses.

Virus

Host

Location

Supporting text

Our findings support a bat origin for MERS-CoV and indicate the need for surveillance of HKU4-related viruses in bats.

Citation context

References

54 references

Reference network

Force-directed citation graph. OmniVira-indexed references are prioritized and recursively expanded up to three steps.

149 nodes · 235 links

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Evidence overview

Evidence 7

Types 4

Virus 3

Host 2

Evidence types

Receptor Usage 3 Molecular Adaptation 2 Genomic Evolution 1 Zoonotic Surveillance 1

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: Cell host & microbe
Volume / Issue / Pages: 16 / 3 / 328-37
ISSN: 1934-6069
Journal country: United States
DOI: 10.1016/j.chom.2014.08.009