A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry

被引：53

作者：

Chen, Jing ^{[1
]}

Yang, Xinglou ^{[1
]}

Si, Haoru ^{[1
,2
]}

Gong, Qianchun ^{[3
,4
,5
]}

Que, Tengcheng ^{[6
,7
]}

Li, Jing ^{[8
]}

Li, Yang ^{[1
]}

Wu, Chunguang ^{[1
,2
]}

Zhang, Wei ^{[1
]}

Chen, Ying ^{[1
,2
]}

Luo, Yun ^{[1
,2
]}

Zhu, Yan ^{[1
]}

Li, Bei ^{[1
]}

Luo, Dongsheng ^{[1
]}

Hu, Ben ^{[1
]}

Lin, Haofeng ^{[1
,2
]}

Jiang, Rendi ^{[3
]}

Jiang, Tingting ^{[1
]}

Li, Qian ^{[1
,2
]}

Liu, Meiqin ^{[1
,2
]}

Xie, Shizhe ^{[1
,2
]}

Su, Jia ^{[1
,2
]}

Zheng, Xiaoshuang ^{[1
,2
]}

Li, Ang ^{[1
,2
]}

Yao, Yulin ^{[1
]}

Yang, Yong ^{[1
,2
]}

Chen, Panyu ^{[6
]}

Wu, Aiqiong ^{[6
]}

He, Meihong ^{[6
]}

Lin, Xinhua ^{[3
,4
,5
]}

Tong, Yigang ^{[8
]}

Hu, Yanling ^{[9
,10
]}

Shi, Zheng-Li ^{[1
]}

Zhou, Peng ^{[1
]}

机构：

[1] Chinese Acad Sci, Wuhan Inst Virol, CAS Key Lab Special Pathogens, Wuhan, Peoples R China

[2] Univ Chinese Acad Sci, Beijing, Peoples R China

[3] Fudan Univ Shanghai, Zhongshan Hosp, Greater Bay Area Inst Precis Med Guangzhou, State Key Lab Genet Engn,Sch Life Sci, Shanghai 200438, Peoples R China

[4] Sichuan Univ, West China Univ Hosp 2, Joint Lab Lung Dev & Related Dis, Chengdu 610041, Peoples R China

[5] Fudan Univ, Sch Life Sci, Chengdu 610041, Peoples R China

[6] Guangxi Zhuang Autonomous Reg Terr Wildlife Med ai, Nanning 530028, Guangxi, Peoples R China

[7] City Univ Macau, Fac Data Sci, Beijing, Peoples R China

[8] Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing Adv Innovat Ctr Soft Matter Sci & Engn, Beijing, Peoples R China

[9] Guangxi Med Univ, Inst Life Sci, Nanning 530021, Guangxi, Peoples R China

[10] Guangzhou Lab, Ctr Genom & Personalized Med, Guangxi Collaborat Innovat Ctr Genom & Personalize, Guangxi Key Lab Genom & Personalized Med, 9 Xing Dao Huan Bei Rd, Guangzhou 530021, Guangdong, Peoples R China

来源：

CELL | 2023年 / 186卷 / 04期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

RESPIRATORY SYNDROME CORONAVIRUS; TO-HUMAN TRANSMISSION; SARS-CORONAVIRUS; RECEPTOR; SPIKE; MUTATIONS; EVOLUTION; ALIGNMENT; USAGE; COV;

D O I：

10.1016/j.cell.2023.01.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleav-age site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.

引用

页码：850 / +

页数：31

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