Isolation of MERS-related coronavirus from lesser bamboo bats that uses DPP4 and infects human-DPP4-transgenic mice

Susanna K. P. Lau (), Rachel Y. Y. Fan, Longchao Zhu, Kenneth S. M. Li, Antonio C. P. Wong, Hayes K. H. Luk, Emily Y. M. Wong, Carol S. F. Lam, George C. S. Lo, Joshua Fung, Zirong He, Felix C. H. Fok, Rex K. H. Au-Yeung, Libiao Zhang, Kin-Hang Kok, Kwok-Yung Yuen and Patrick C. Y. Woo ()
Additional contact information
Susanna K. P. Lau: The University of Hong Kong
Rachel Y. Y. Fan: The University of Hong Kong
Longchao Zhu: The University of Hong Kong
Kenneth S. M. Li: The University of Hong Kong
Antonio C. P. Wong: The University of Hong Kong
Hayes K. H. Luk: The University of Hong Kong
Emily Y. M. Wong: The University of Hong Kong
Carol S. F. Lam: The University of Hong Kong
George C. S. Lo: The University of Hong Kong
Joshua Fung: The University of Hong Kong
Zirong He: The University of Hong Kong
Felix C. H. Fok: The University of Hong Kong
Rex K. H. Au-Yeung: The University of Hong Kong
Libiao Zhang: Guangdong Institute of Applied Biological Resources
Kin-Hang Kok: The University of Hong Kong
Kwok-Yung Yuen: The University of Hong Kong
Patrick C. Y. Woo: The University of Hong Kong

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract While a number of human coronaviruses are believed to be originated from ancestral viruses in bats, it remains unclear if bat coronaviruses are ready to cause direct bat-to-human transmission. Here, we report the isolation of a MERS-related coronavirus, Tylonycteris-bat-CoV-HKU4, from lesser bamboo bats. Tylonycteris-bat-CoV-HKU4 replicates efficiently in human colorectal adenocarcinoma and hepatocarcinoma cells with cytopathic effects, and can utilize human-dipeptidyl-peptidase-4 and dromedary camel-dipeptidyl-peptidase-4 as the receptors for cell entry. Flow cytometry, co-immunoprecipitation and surface plasmon resonance assays show that Tylonycteris-bat-CoV-HKU4-receptor-binding-domain can bind human-dipeptidyl-peptidase-4, dromedary camel-dipeptidyl-peptidase-4, and Tylonycteris pachypus-dipeptidyl-peptidase-4. Tylonycteris-bat-CoV-HKU4 can infect human-dipeptidyl-peptidase-4-transgenic mice by intranasal inoculation with self-limiting disease. Positive virus and inflammatory changes were detected in lungs and brains of infected mice, associated with suppression of antiviral cytokines and activation of proinflammatory cytokines and chemokines. The results suggest that MERS-related bat coronaviruses may overcome species barrier by utilizing dipeptidyl-peptidase-4 and potentially emerge in humans by direct bat-to-human transmission.

Date: 2021
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DOI: 10.1038/s41467-020-20458-9

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