《2018 Receptor usage of a novel bat lineage C betacoronavirus reveals evolution of MERS-related coronavirus spike protein》由会员分享，可在线阅读，更多相关《2018 Receptor usage of a novel bat lineage C betacoronavirus reveals evolution of MERS-related coronavirus spike protein（34页珍藏版）》请在金锄头文库上搜索。
1、Accepted Manuscript The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: . Receptor usage of a novel bat lineage C betacoronavirus reveals evolution of MERS-related coronavirus spike proteins for human
2、DPP4 binding Susanna K. P. Lau,1,2,3,4,a* Libiao Zhang,5,6,7,a Hayes K. H. Luk,4,a Lifeng Xiong,4,a Xingwen Peng,5,6,7 Kenneth S. M. Li,4 Xiangyang He,5,6,7 Pyrear Su-Hui Zhao,4 Rachel Y. Y. Fan,4 Antonio C. P. Wong,4 Syed Shakeel Ahmed,4 Jian-Piao Cai,4 Jasper F. W. Chan,1,2,3,4 Yinyan Sun,8 Dongya
3、n Jin,9 Honglin Chen,1,2,3,4 Terrence C. K. Lau,10 Raven K. H. Kok,1,2,3,4 Wenhui Li,8 Kwok-Yung Yuen,1,2,3,4 Patrick C. Y. Woo1,2,3,4* 1 State Key Laboratory of Emerging Infectious Diseases. 2 Department of Microbiology. 3 Carol Yu Centre for Infection. 4 Collaborative Innovation Center for Diagnos
4、is and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; 5 Guangdong Key Laboratory of Animal Conservation and Resource Utilization. 6 Guangdong Public Laboratory of Wild Animal Conservation and Utilization. 7 Guangdong Institute of App
5、lied Biological Resources, Guangzhou, China, Guangzhou, Guangdong Province, China; 8 National Institute of Biological Sciences, Zhongguancun Life Science Park, Changping, Beijing, China; 9 School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China; 10 Department of Biomedical Scien
6、ces, City University of Hong Kong, Hong Kong, China. Downloaded from by guest on 20 January 2018 Accepted Manuscript 2 *Address for correspondence: Patrick CY Woo, State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Room 423, University Path
7、ology Building, Queen Mary Hospital, Hong Kong, China. E-mail: pcywoohku.hk; Susanna KP Lau, State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Room 423, University Pathology Building, Queen Mary Hospital, Hong Kong, China. E-mail: skplauhk
8、u.hk aS.K.P.L, L.Z, H.K.H.L and L.X contributed equally to the manuscript. Running title: A novel MERS-related CoV Summary: The discovery of Hp-BatCoV HKU25 bridges the evolutionary gap between MERS-CoV and existing bat viruses, and suggests that bat viruses may have evolved to generate MERS-CoV thr
9、ough modulation of the spike protein for binding to hDPP4. Downloaded from by guest on 20 January 2018 Accepted Manuscript 3 Abstract Although bats are known to harbor MERS-CoV-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-re
10、lated betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. While being 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. Since Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can utilize MERS-Co
11、V receptor, hDPP4, for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and utilize hDPP4. HKU25-RBD can bind to hDPP4 protein and hDPP4-expressing cells, but with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can utilize hDPP4 for entry to hDPP4-expr
12、essing cells, though with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat coronavirus spike proteins may have evolved in a stepwise manner for binding to hDPP4. Keywords: Middle East Respiratory Syndrome Coronavirus, Spike g
13、lycoprotein, Dipeptidyl peptidase 4, Hypsugo bat Downloaded from by guest on 20 January 2018 Accepted Manuscript 4 Introduction The Middle East Respiratory Syndrome (MERS) has affected 27 countries in four continents with 2090 cases and a fatality rate of 34.9% since its emergence in 2012. The etiol
14、ogical agent, MERS coronavirus (MERS-CoV), belongs to Betacoronavirus lineage C 1, 2 and utilizes human dipeptidyl peptidase 4 (hDPP4) as receptor for cell entry 3. While dromedaries are likely the immediate animal source of the epidemic 4-6, bats also harbor MERS-CoV-related viruses which may sugge
15、st a possible bat origin 7-13. However, the evolutionary pathway and direct ancestor of MERS-CoV remains obscure. In particular, there is an evolutionary gap between MERS-CoV and related bat viruses. Since the SARS epidemic, numerous novel CoVs have been discovered 14-16, with bats uncovered as an i
16、mportant reservoir for alphacoronaviruses and betacoronaviruses 17-21. When MERS-CoV was first discovered, it was most closely related to Tylonycteris bat CoV HKU4 (Ty-BatCoV HKU4) and Pipistrellus bat CoV HKU5 (Pi-BatCoV HKU5) previously discovered in Lesser bamboo bat (Tylonycteris pachypus) and Japanese pipistrelle (Pipistrellus abramus) respectively in Hong Kong 1, 7-10, 22. The spike of Ty-BatCoV HKU4,
