Severe acute respiratory syndrome coronavirus type 1 (SARS-CoV-1) M protein is a glycosylated structural protein with three transmembrane (TM) domains. M protein predominantly localizes to the Golgi complex and is essential for the assembly of viral particles. SARS-CoV-1 M protein was found to suppress production of type I IFNs in human embryonic kidney 293 cells (HEK293 cells) expressing RIG-I (DDX58), MDA5 (IFIH1), TRAF3, TBK1 and IKKε (IKBKE) proteins (Siu KL et al. 2009; 2014). IFN antagonism was mediated by N-terminal TM1 domain of SARS-CoV-1 M protein (amino acids 1–38), which targets M protein to the Golgi complex (Siu KL et al. 2014). Co-immunoprecipitation analysis revealed that TM1 of M protein interacted with TRAF3, RIG-I (DDX58), TBK1 and IKBKE (Siu KL et al. 2014) in HEK293 expressing tagged proteins (Siu KL et al. 2014). SARS-CoV-1 M protein is thought to prevent the formation of the TRAF3:TANK:TBK1/IKBKE complex and thereby inhibits TBK1/IKBKE-dependent activation of IRF3/IRF7 transcription factors (Siu KL et al. 2009; 2014). The Reactome event shows binding of SARS-CoV-1 M protein to TRAF3. This binding prevents TRAF3 from interacting with downstream effectors TANK, TBK1 and IKBKE (IKKε). However, it remains to be clarified how the Golgi-associated M protein might contribute to the suppression of IRF3/IRF7 activation under the DDX58:MAVS antiviral signaling axis.