IRF3 and herpes simplex encephalitis: Activated STING travels through the ER, trans-Golgi network (TGN) and endosomes, which activates IRF3 in a TBK1-dependent manner to stimulate IFN and inflammatory cytokine production (Figure 2; Reinert et al., 2016; Fang et al., 2023; Qin et al., 2023) To assess the role of cGAS-STING pathway in HSV-1 infection, Reinert et al. (2016) used cGAS- and STING-deficient mice and found that these mice were highly susceptible to HSV-1 infection and succumbed to herpes simplex encephalitis (HSE).