Post-translational modifications of coronavirus proteins: roles and function

Fung, To Sing; Liu, Ding Xiang

PTMs contribute significantly to the functions of coronavirus proteins. Apart from facilitating the folding and intracellular trafficking of the coronavirus S protein, N-linked glycans also constitute a significant part of the protein mass and profoundly affect the conformation of the mature S protein and its binding to surface receptors. N-linked glycans may play a role in the antigenicity of S protein, and glycosylation may also contribute to the induction of innate immune response, thereby affecting the viral pathogenesis. Phosphorylation of coronavirus N protein improves its selective binding to viral RNA and may regulate the uncoating and assembly process during replication. Importantly, the phosphorylation status of MHV-JHM N protein, controlled by the host kinase GSK-3, acts as a switch to regulate genome replication/transcription, although a similar mechanism has not been described for other coronaviruses. Coronavirus also employ multiple mechanisms to interfere with PTMs of host proteins. In particular, the DUB and deISGylating activities encoded by nsp3 suppress the induction and signaling of type I interferons.