Specific asparagine-linked glycosylation sites are critical for DC-SIGN- and L-SIGN-mediated severe acute respiratory syndrome coronavirus entry.
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.
Han
Dong P
DP
Case Western Reserve University School of Medicine, Department of Medicine, Division of Infectious Diseases, 10900 Euclid Avenue, Cleveland, OH 44106-4984, USA.
Lohani
Motashim
M
Cho
Michael W
MW
D000595:Amino Acid Sequence; D000818:Animals; D001216:Asparagine / Q000737:chemistry*; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D002522:Chlorocebus aethiops; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D037102:Lectins / Q000737:chemistry; D037181:Lectins, C-Type / Q000737:chemistry*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011956:Receptors, Cell Surface / Q000737:chemistry*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D045169:Severe Acute Respiratory Syndrome / Q000821:virology*; D014709:Vero Cells; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D001216:Asparagine; D015815:Cell Adhesion Molecules; D037102:Lectins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human
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