Modulation of cell signalling by human coronavirus HKU1 S and M proteins.

In 2003, an outbreak of severe acute respiratory syndrome (SARS) occurred in Hong Kong and spread worldwide. The SARS coronavirus (SARCoV) caused a highly lethal disease and disproved the concept that human coronaviruses are generally associated with mild respiratory disease. Another new coronavirus—HCoV-HKU1—that circulates commonly in the human population and causes relatively milder respiratory tract illness worldwide was also discovered.1 The mechanism by which SARS-CoV and HCoV-HKU1 cause respiratory diseases of different severity remains elusive. Variations in their ability to modulate cell signalling and innate immunity might be influential.2 Human coronaviruses are enveloped and positive-stranded RNA viruses with a large genome. They hijack the endoplasmic reticulum (ER) to process their structural and non-structural proteins produced in extraordinarily large amounts. They also need to circumvent the production and function of type I interferons (IFNs), major effectors of innate antiviral immunity. We have demonstrated the capability of SARS-CoV S protein to induce ER stress and to activate the unfolded protein response (UPR).3 We have also found that SARSCoV M protein suppresses innate IFN production by impeding the formation of a functional complex of tumour necrosis factor receptor-associated factor 3 (TRAF3) TRAF family member-associated NF-κB activator (TANK) TANK-binding kinase Hong Kong Med J 2016;22(Suppl 4):S22-4 RFCID project number: 10091192