Identification of a Novel Betacoronavirus (Merbecovirus) in Amur Hedgehogs from China.

Susanna K P Lau1,2,3,4 Hayes K H Luk5 Antonio C P Wong6 Rachel Y Y Fan7 Carol S F Lam8 Kenneth S M Li9 Syed Shakeel Ahmed10 Franklin W N Chow11 Jian-Piao Cai12 Xun Zhu13,14 Jasper F W Chan15,16,17,18 Terrence C K Lau19 Kaiyuan Cao20,21 Mengfeng Li22,23 Patrick C Y Woo24,25,26,27 Kwok-Yung Yuen28,29,30,31
Affiliations 31 institutions
  1. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  2. State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  3. Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  4. Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  5. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  6. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  7. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  8. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  9. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  10. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  11. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  12. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  13. Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. [email protected].
  14. Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China. [email protected].
  15. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  16. State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  17. Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  18. Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  19. Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong 999077, China. [email protected].
  20. Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. [email protected].
  21. Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China. [email protected].
  22. Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. [email protected].
  23. Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China. [email protected].
  24. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  25. State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  26. Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  27. Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  28. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  29. State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  30. Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong 999077, China. [email protected].
  31. Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong 999077, China. [email protected].

Abstract

While dromedaries are the immediate animal source of Middle East Respiratory Syndrome (MERS) epidemic, viruses related to MERS coronavirus (MERS-CoV) have also been found in bats as well as hedgehogs. To elucidate the evolution of MERS-CoV-related viruses and their interspecies transmission pathway, samples were collected from different mammals in China. A novel coronavirus related to MERS-CoV, Erinaceus amurensis hedgehog coronavirus HKU31 (Ea-HedCoV HKU31), was identified from two Amur hedgehogs. Genome analysis supported that Ea-HedCoV HKU31 represents a novel species under Merbecovirus, being most closely related to Erinaceus CoV from European hedgehogs in Germany, with 79.6% genome sequence identity. Compared to other members of Merbecovirus, Ea-HedCoV HKU31 possessed unique non-structural proteins and putative cleavage sites at ORF1ab. Phylogenetic analysis showed that Ea-HedCoV HKU31 and BetaCoV Erinaceus/VMC/DEU/2012 were closely related to NeoCoV and BatCoV PREDICT from African bats in the spike region, suggesting that the latter bat viruses have arisen from recombination between CoVs from hedgehogs and bats. The predicted HKU31 receptor-binding domain (RBD) possessed only one out of 12 critical amino acid residues for binding to human dipeptidyl peptidase 4 (hDPP4), the MERS-CoV receptor. The structural modeling of the HKU31-RBD-hDPP4 binding interphase compared to that of MERS-CoV and Tylonycteris bat CoV HKU4 (Ty-BatCoV HKU4) suggested that HKU31-RBD is unlikely to bind to hDPP4. Our findings support that hedgehogs are an important reservoir of Merbecovirus, with evidence of recombination with viruses from bats. Further investigations in bats, hedgehogs and related animals are warranted to understand the evolution of MERS-CoV-related viruses.

Supporting text Virus Host Location
China 230 coronavirus 195 hedgehog 3 Merbecovirus 12 novel species 2 Animals 1948 Betacoronavirus 78 China 229 Chiroptera 371 Coronavirus Infections 171 Dipeptidyl Peptidase 4 32 Disease Reservoirs 149 Evolution, Molecular 176 Genome, Viral 317 Hedgehogs 6 Humans 1440 Phylogeny 805

Evidence records

3 total
Zoonotic Surveillance
2 records · 2 evidence types
Evidence type
1 records
OVE3478
Key finding

A novel coronavirus, Erinaceus amurensis hedgehog coronavirus HKU31, related to MERS-CoV, was detected in Amur hedgehogs sampled in China.

Virus
Host
Location
Supporting text

Samples were collected from different mammals in China. A novel coronavirus related to MERS-CoV, Erinaceus amurensis hedgehog coronavirus HKU31 (Ea-HedCoV HKU31), was identified from two Amur hedgehogs.

Method
identification | genome analysis
Geographic raw
China
Country inferred
CHN
Evidence type
1 records
OVE3482
Key finding

Hedgehogs are identified as an important reservoir of Merbecovirus, with evidence of recombination involving bat viruses.

Virus
Host
Location
Not specified
Supporting text

Our findings support that hedgehogs are an important reservoir of Merbecovirus, with evidence of recombination with viruses from bats.

Method
phylogenetic analysis | genome analysis
Sample type
samples from hedgehogs
Genomic Evolution
1 records · 1 evidence types
Evidence type
1 records
OVE3479
Key finding

Genome analysis showed that Ea-HedCoV HKU31 forms a novel Merbecovirus species most closely related to Erinaceus CoV from European hedgehogs in Germany, sharing 79.6% genome sequence identity.

Virus
Host
Location
Not specified
Supporting text

Genome analysis supported that Ea-HedCoV HKU31 represents a novel species under Merbecovirus, being most closely related to Erinaceus CoV from European hedgehogs in Germany, with 79.6% genome sequence identity.

Genes or proteins
genome
Analysis methods
genome analysis