Post-translational modifications of coronavirus proteins: roles and function

Fung, To Sing; Liu, Ding Xiang

Although not essential for its binding to the cellular receptor ACE2, N-linked glycosylation of SARS-CoV may still contribute to efficient attachment of virions to the host cells. The C-type lectin DC-SIGN was shown to facilitate cell entry of SARS-CoV [58, 59] . The DC-SIGN binding region was mapped to amino acid residues 324-386 of SARS-CoV, and pseudotyped viruses with mutated N-linked glycosylation sites (N330Q or N357Q) had significantly reduced DC-SIGN-binding capacity [60] . In a separate study, seven glycosylation sites (N109, N118, N119, N158, N227, N589 and N699) in SARS-CoV S protein were also shown to be critical for virus entry mediated by the DC-SIGN and/or L-SIGN [61] . The interaction between N-linked glycans and lectins can also negatively affect receptor binding of coronavirus. For example, mannose-binding lectin was shown to interact with SARS-CoV S-pseudotyped virus and block viral binding to DC-SIGN, and N-linked glycosylation at N330 was found critical for the specific interaction between mannose-binding lectin and SARS-CoV S protein [62] . Since N330 is also critical for DC-SIGN-binding, competitive binding between the two lectins to N-linked glycans on SARS-CoV S protein may have some implications in the attachment and entry of virions. At last, LSECtin, a lectin coexpressed with DC-SIGN on sinusoidal endothelial cells in the liver and lymph node, was also shown to interact with SARS-CoV S-pseudotyped virus [63] .