Email updates

Keep up to date with the latest news and content from Cell & Bioscience and BioMed Central.

Open Access Open Badges Research

Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1

Kam-Leung Siu1, Ching-Ping Chan1, Kin-Hang Kok1, Patrick C-Y Woo2 and Dong-Yan Jin1*

Author Affiliations

1 Department of Biochemistry, The University of Hong Kong, 3/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong

2 Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong

For all author emails, please log on.

Cell & Bioscience 2014, 4:3  doi:10.1186/2045-3701-4-3

Published: 13 January 2014



Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). It is not understood whether HCoV-HKU1 S protein has similar activity. In addition, the UPR-activating domain in SARS-CoV S protein remains to be identified.


In this study we compared S proteins of SARS-CoV and HCoV-HKU1 for their ability to activate the UPR. Both S proteins were found in the endoplasmic reticulum. Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. Both S proteins showed a similar pattern of UPR-activating activity. Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. N-linked glycosylation was not required for the activation of the UPR by S proteins. S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 was capable of activating the UPR. A central region (amino acids 201–400) of SARS-CoV S1 was required for this activity.


SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling.

SARS coronavirus; Human coronavirus HKU1; Spike; ER stress; Unfolded protein response