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Journal of Virology, September 2006, p. 9279-9287, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00659-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Modulation of the Unfolded Protein Response by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein

Ching-Ping Chan,1 Kam-Leung Siu,1 King-Tung Chin,1 Kwok-Yung Yuen,2 Bojian Zheng,2 and Dong-Yan Jin1*

Departments of Biochemistry,1 Microbiology,, The University of Hong Kong, Hong Kong, China2

Received 1 April 2006/ Accepted 29 June 2006

Perturbation of the function of endoplasmic reticulum (ER) causes stress leading to the activation of cell signaling pathways known as the unfolded protein response (UPR). Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) uses ER as a site for synthesis and processing of viral proteins. In this report, we demonstrate that infection with SARS-CoV induces the UPR in cultured cells. A comparison with M, E, and NSP6 proteins indicates that SARS-CoV spike (S) protein sufficiently induces transcriptional activation of several UPR effectors, including glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein. A substantial amount of S protein accumulates in the ER. The expression of S protein exerts different effects on the three major signaling pathways of the UPR. Particularly, it induces GRP78/94 through PKR-like ER kinase but has no influence on activating transcription factor 6 or X box-binding protein 1. Taken together, our findings suggest that SARS-CoV S protein specifically modulates the UPR to facilitate viral replication.

* Corresponding author. Mailing address: Department of Biochemistry, The University of Hong Kong, 3/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong. Phone: 852-2819-9491. Fax: 852-2855-1254. E-mail: dyjin{at}hkucc.hku.hk.

Journal of Virology, September 2006, p. 9279-9287, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00659-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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