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Journal of Virology, November 2007, p. 12029-12039, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00315-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Specific Asparagine-Linked Glycosylation Sites Are Critical for DC-SIGN- and L-SIGN-Mediated Severe Acute Respiratory Syndrome Coronavirus Entry{triangledown}

Dong P. Han,1 Motashim Lohani,1 and Michael W. Cho1,2,3*

Departments of Medicine,1 Biochemistry,2 Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio 441063

Received 12 February 2007/ Accepted 11 August 2007

Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus (CoV) designated SARS-CoV. The virus utilizes angiotensin-converting enzyme 2 (ACE2) as the primary receptor. Although the idea is less clear and somewhat controversial, SARS-CoV is thought to use C-type lectins DC-SIGN and/or L-SIGN (collectively referred to as DC/L-SIGN) as alternative receptors or as enhancer factors that facilitate ACE2-mediated virus infection. In this study, the function of DC/L-SIGN in SARS-CoV infection was examined in detail. The results of our study clearly demonstrate that both proteins serve as receptors independently of ACE2 and that there is a minimal level of synergy between DC/L-SIGN and ACE2. As expected, glycans on spike (S) glycoprotein are important for DC/L-SIGN-mediated virus infection. Site-directed mutagenesis analyses have identified seven glycosylation sites on the S protein critical for DC/L-SIGN-mediated virus entry. They include asparagine residues at amino acid positions 109, 118, 119, 158, 227, 589, and 699, which are distinct from residues of the ACE2-binding domain (amino acids 318 to 510). Amino acid sequence analyses of S proteins encoded by viruses isolated from animals and humans suggest that glycosylation sites N227 and N699 have facilitated zoonotic transmission.

* Corresponding author. Mailing address: Case Western Reserve University School of Medicine, Department of Medicine, Division of Infectious Diseases, 10900 Euclid Ave., Cleveland, OH 44106-4984. Phone: (216) 368-1221. Fax: (216) 368-0069. E-mail: mcho{at}case.edu

{triangledown} Published ahead of print on 22 August 2007.

Journal of Virology, November 2007, p. 12029-12039, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00315-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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