Figure 9. The multifaceted m152 protein selectively modulates STING‐dependent type I IFN, but not NF‐κB, signaling.

1. Upon stimulation with DNA or by viral infection, the pattern recognition receptor (PRR) cGAS produces the second messenger 2′3′‐cGAMP, which binds to the ER‐resident protein STING. STING then dimerizes and translocates from the ER to the Golgi, from where it activates the signaling pathway leading to induction of type I IFN via the kinase TBK1 and the IRF3 transcription factor. cGAS‐STING signaling also induces activation of the NF‐κB transcription factor, leading to proinflammatory cytokine expression, but from which subcellular compartment this signaling pathway is initiated is not understood.
2. The viral type I membrane protein m152 is expressed immediately after MCMV infection. m152 binds STING in the ER via their respective luminal domains and traffics with STING to the Golgi. In the presence of m152, trafficking of STING is delayed, leading to a reduced type I IFN, but intact NF‐κB, response. Mutation of K288 in STING results in a STING mutant that cannot leave the ER and thereby cannot activate the type I IFN response, but is still able to induce the NF‐κB pathway. These results suggest that STING induces the NF‐κB pathway from the ER, prior to its trafficking to the Golgi.