Cell Entry of Porcine Epidemic Diarrhea Coronavirus Is Activated by Lysosomal Proteases

Porcine epidemic diarrhea coronavirus (PEDV) is currently devastating the United States pork industry by causing an 80–100% fatality rate in infected piglets. Coronavirus spike proteins mediate virus entry into cells, a process that requires the spike proteins to be proteolytically activated. It has...

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Bibliographic Details
Published in:The Journal of biological chemistry 2016-11, Vol.291 (47), p.24779-24786
Main Authors: Liu, Chang, Ma, Yuanmei, Yang, Yang, Zheng, Yuan, Shang, Jian, Zhou, Yusen, Jiang, Shibo, Du, Lanying, Li, Jianrong, Li, Fang
Format: Article
Language:English
Subjects:
Animals
Cathepsin B - metabolism
Cathepsin L - metabolism
Cell Line
cysteine protease
Humans
Lysosomes - enzymology
Lysosomes - virology
membrane fusion
Microbiology
Porcine epidemic diarrhea virus - physiology
protease inhibitor
proteolysis
Spike Glycoprotein, Coronavirus - metabolism
Swine
virus entry
Virus Internalization
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Summary:Porcine epidemic diarrhea coronavirus (PEDV) is currently devastating the United States pork industry by causing an 80–100% fatality rate in infected piglets. Coronavirus spike proteins mediate virus entry into cells, a process that requires the spike proteins to be proteolytically activated. It has been a conundrum which proteases activate PEDV entry. Here we systematically investigated the roles of different proteases in PEDV entry using pseudovirus entry, biochemical, and live virus infection assays. We found that the PEDV spike is activated by lysosomal cysteine proteases but not proprotein convertases or cell surface serine proteases. Extracellular trypsin activates PEDV entry when lysosomal cysteine proteases are inhibited. We further pinpointed cathepsin L and cathepsin B as the lysosomal cysteine proteases that activate the PEDV spike. These results advance our understanding of the molecular mechanism for PEDV entry and identify potential antiviral targets for curbing the spread of PEDV.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M116.740746