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Open Access 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

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

Published: 13 January 2014

Abstract

Background

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.

Results

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.

Conclusions

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

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