Our observation here that cGAS-STING-TBK1 signaling promotes VPA-responsive IE gene expression during the establishment of HCMV latency suggests that PRR detection and signaling could protect against latent infection by both inducing an IFN-I response and promoting the expression of viral antigens that can render infected cells visible to adaptive responses. Here, TBK1 is linked to disease arising from reactivation of latent virus.