β-Catenin Is Required for the cGAS/STING Signaling Pathway but Antagonized by the Herpes Simplex Virus 1 US3 Protein

• DOI: 10.1128/jvi.01847-19
• Publication Date: 2019-12-04T13:23:56Z
• Authors: Hongjuan You; Yingying Lin; Feng Lin; Mingyue Yang; Jiahui Li; Rongzhao Zhang; Zhiming Huang; Qingtang Shen; Renxian Tang; Chunfu Zheng
• Keywords: 0303 health sciences; Down-Regulation; Membrane Proteins; Herpesvirus 1, Human; Protein Serine-Threonine Kinases; Nucleotidyltransferases; Immunity, Innate; 3. Good health; Gene Knockout Techniques; Viral Proteins; 03 medical and health sciences; HEK293 Cells; A549 Cells; Chlorocebus aethiops; Interferon Type I; Animals; Cytokines; Humans; Phosphorylation; Vero Cells; beta Catenin; Signal Transduction

Although increasing evidence has demonstrated that HSV-1 subverts host immune responses and establishes lifelong latent infection, the molecular mechanisms by which HSV-1 interrupts antiviral innate immunity, especially the cGAS/STING-mediated cellular DNA-sensing signaling pathway, have not been fully explored. Here, we show that β-catenin promotes cGAS/STING-mediated activation of the IFN pathway, which is important for cellular innate immune responses and intrinsic resistance to DNA virus infection. The protein kinase US3 antagonizes the production of IFN by targeting β-catenin via its kinase activity. The findings in this study reveal a novel mechanism for HSV-1 to evade host antiviral immunity and add new knowledge to help in understanding the interaction between the host and HSV-1 infection.