FIG 8.

A working model on UL94-mediated HCMV immune evasion. Cytosolic DNA sensor cGAS recognizes HCMV DNA and synthesizes the second messenger cGAMP. cGAMP binds to MITA, facilitating the dimerization and oligomerization of MITA, and initiates translocation of MITA from the ER to perinuclear microsomes. During this process, MITA recruits TBK1 and IRF3, leading to phosphorylation and activation of IRF3 by TBK1. HCMV protein UL94 disrupts MITA dimerization and recruitment of TBK1 and therefore inhibits the MITA-mediated innate immune response against HCMV infection.