Putative conformations of the receptor-binding domain in S protein of hCoV-EMC in complex with its receptor dipeptidyl peptidase-4.
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ABSTRACT:
SUBMITTER: Jiang S
PROVIDER: S-EPMC4355062 | biostudies-literature | 2013 Aug
REPOSITORIES: biostudies-literature
Publications
Putative conformations of the receptor-binding domain in S protein of hCoV-EMC in complex with its receptor dipeptidyl peptidase-4.
Jiang Shibo S Lu Lu L Du Lanying L Debnath Asim K AK
The Journal of infection 20130417 2
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Project description:Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread. Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection. Viral genome analysis revealed close relatedness to coronaviruses found in bats. Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.
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2013-08-29 | GSE44542 | GEO
Project description:Microarray analysis of peripheral blood mononuclear cells (PBMCs), lungs, and lung lesions collected over the course of hCoV-EMC infection of 6 rhesus macaques. 6 rhesus macaques were infected intratracheally with hCoV-EMC. PBMCs were collected at days 0, 1, 3, and 6, and lungs were collected from serial sacrifices of 3 animals each at day 3 and day 6. Infection produced a mild-moderate, self-limiting respiratory infection, and was not lethal. We performed microarray analysis (using Agilent Rhesus arrays) on all lungs, lung lesions, and PBMCs collected for the study.
2013-08-29 | E-GEOD-44542 | biostudies-arrayexpress
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