A single asparagine-linked glycosylation site of the severe acute respiratory syndrome coronavirus spike glycoprotein facilitates inhibition by mannose-binding lectin through multiple mechanisms.
Mannose-binding lectin (MBL) is a serum protein that plays an important role in host defenses as an opsonin and through activation of the complement system. The objective of this study was to assess the interactions between MBL and severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) glycoprotein (SARS-S). MBL was found to selectively bind to retroviral particles pseudotyped with SARS-S. Unlike several other viral envelopes to which MBL can bind, both recombinant and plasma-derived human MBL directly inhibited SARS-S-mediated viral infection. Moreover, the interaction between MBL and SARS-S blocked viral binding to the C-type lectin, DC-SIGN. Mutagenesis indicated that a single N-linked glycosylation site, N330, was critical for the specific interactions between MBL and SARS-S. Despite the proximity of N330 to the receptor-binding motif of SARS-S, MBL did not affect interactions with the ACE2 receptor or cathepsin L-mediated activation of SARS-S-driven membrane fusion. Thus, binding of MBL to SARS-S may interfere with other early pre- or postreceptor-binding events necessary for efficient viral entry.
Zhou
Yanchen
Y
Blood Systems Research Institute and Department of Laboratory Medicine, University of California, San Francisco, California 94118, USA.
Lu
Kai
K
Pfefferle
Susanne
S
Bertram
Stephanie
S
Glowacka
Ilona
I
Drosten
Christian
C
Pöhlmann
Stefan
S
Simmons
Graham
G
D000328:Adult; D000368:Aged; D020816:Amino Acid Motifs; D001216:Asparagine / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006031:Glycosylation; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045169:Severe Acute Respiratory Syndrome / Q000378:metabolism* / Q000821:virology; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D001216:Asparagine; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D037601:Mannose-Binding Lectin; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin