Post-translational modifications of coronavirus proteins: roles and function

Fung, To Sing; Liu, Ding Xiang

Interestingly, some of the known cellular receptors for coronavirus have also been shown to be modified by glycosylation. N-linked glycosylation of CEACAM1, the cellular receptor protein of MHV, was found essential for its binding to MHV-A59 virions [67] , although recombinant proteins with mutations in the three N-linked glycosylation sites in the N-terminal domain were still functional [68] . On the other hand, insertion of an N-linked glycosylation site into human APN, the receptor for HCoV-229E, abolished its activity to bind HCoV-229E virions [69] . Similarly, N-linked glycosylation of DPP4, the cognate receptor of MERS-CoV, dramatically affects its binding to MERS-CoV S protein. Normally, mouse DPP4 does not support MERS-CoV entry. However, when the N328 glycosylation site was mutated in the presence of a secondary mutation A288L, the binding affinity of mouse DPP4 to MERS-CoV was significantly increased [70] . Conversely, when the corresponding glycosylation site was introduced to human DPP4, the binding of MERS-CoV was significantly reduced [70] . Therefore, glycosylation of coronavirus receptors contributes significantly to the host tropism of coronavirus infection, although additional sequence and structural determinants of S protein are also involved [71] .