Cell entry of porcine epidemic diarrhea coronavirus is activated by lysosomal proteases

Chang Liu, Yuanmei Ma, Yang Yang, Yuan Zheng, Jian Shang, Yusen Zhou, Shibo Jiang, Lanying Du, Jianrong Li, Fang Li

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)24779-24786
Number of pages8
JournalJournal of Biological Chemistry
Issue number47
StatePublished - Nov 18 2016

Bibliographical note

Funding Information:
This work was supported by NIAID, National Institutes of Health Grants R01AI089728 (to F. L). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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