OmniVira

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

Qihui Wang1 Jianxun Qi1 Yuan Yuan2,3 Yifang Xuan4 Pengcheng Han5 Yuhua Wan2,6 Wei Ji7 Yan Li1 Ying Wu1 Jianwei Wang8 Aikichi Iwamoto9,10 Patrick C Y Woo11,12 Kwok-Yung Yuen11,13,14 Jinghua Yan1 Guangwen Lu1 George F Gao2,15,16,17,18,19
Affiliations 19 institutions
  1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  2. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
  3. School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui Province, China.
  4. Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
  5. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  6. School of Life Sciences, Anhui University, Hefei 230039, China.
  7. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
  8. MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
  9. China-Japan Joint Laboratory of Molecular Microbiology and Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
  10. 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.
  11. State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China
  12. Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China.
  13. Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China
  14. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
  15. School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui Province, China
  16. Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China
  17. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China
  18. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China
  19. Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. Electronic address: [email protected].
PMID25211075 DOI10.1016/j.chom.2014.08.009 Year2014 Journal Cell host & microbe Cell Host Microbe Languageeng Statusppublish

Abstract

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.

Supporting text Virus Host Location
Amino Acid Sequence 128 Animals 1948 Chiroptera 371 Coronavirus 92 Coronavirus Infections 171 Dipeptidyl Peptidase 4 32 Humans 1440 Middle East Respiratory Syndrome Coronavirus 68 Molecular Sequence Data 160 Phylogeny 805 Protein Binding 193 Receptors, Virus 204 Sequence Alignment 51 Spike Glycoprotein, Coronavirus 274

Evidence records

3 total
Functional Mechanism
2 records · 2 evidence types
Evidence type Receptor Usage
1 records
OVE1831 Receptor Usage
Key finding

Bat coronavirus HKU4 spike binds to human CD26 and mediates cell entry via hCD26 recognition, demonstrating functional receptor usage shared with MERS-CoV.

Virus
bat coronavirus HKU4
Host
human Homo sapiens Experimental system
Location
Not specified
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
receptor-binding assay | pseudovirus infection assay | structural analysis of RBD–hCD26 complex
Receptors
human CD26 | hCD26
Evidence type Molecular Adaptation
1 records
OVE1832 Molecular Adaptation
Key finding

The HKU4 receptor-binding domain is structurally less adapted to human CD26 than the MERS-CoV RBD, resulting in lower receptor binding affinity.

Virus
bat coronavirus HKU4 Middle East Respiratory Syndrome Coronavirus
Host
Not specified
Location
Not specified
Supporting text

HKU4-RBD, however, is less adapted to hCD26 than MERS-RBD, explaining its lower affinity for receptor binding.

Genes or proteins
receptor-binding domain | RBD | spike protein
Receptors
human CD26 | hCD26
Mechanism types
receptor binding | host-range expansion
Genomic Evolution
1 records · 1 evidence types
Evidence type Phylogenetic Evolution
1 records