Hong Kong Med J 2016;22(Suppl 4):S22-4
Modulation of cell signalling by human coronavirus HKU1 S and M proteins
DY Jin, PCY Woo
School of Biomedical Sciences, The University of Hong Kong
1. S proteins of both SARS-CoV and HCoV-HKU1 share a similar profile of unfolded protein response (UPR)–activating activity. They activate the production of UPR effector proteins Grp78/94 and to a lesser extent CHOP through PERK kinase.
2. S proteins of SARS-CoV and HCoV-HKU1 have distinct UPR-activating domains. Whereas the UPR-activating activity requires the central region (amino acids 201-400) of the S1 subunit in SARS-CoV, the corresponding part in the HCoV-HKU1 S protein does not induce endoplasmic reticulum stress or UPR.
3. Suppression of type I interferon (IFN) production is a unique property of SARS-CoV M protein. HCoV-HKU1 M protein does not inhibit the innate IFN response.
4. IFN antagonism of SARS-CoV M protein is ascribed to its first transmembrane domain (TM1) situated at the N terminus. TM1 targets M protein to the Golgi complex and interacts with TRAF3 and other transducer proteins to prevent the formation of a functional TRAF3-containing multi-component complex.