Sirt1 Negatively Regulates Cellular Antiviral Responses by Preventing the Cytoplasmic Translocation of Interferon-Inducible Protein 16 in Human Cells
Jie Wang, Xiao Qin, Yulu Huang, Ge Zhang, Yue Liu, Yuhan Cui, Yi Wang, Jinyong Pei, Shujun Ma, Zhishan Song, Xiaofei Zhu, Hui Wang, Bo Yang
Abstract
DNA viruses, such as hepatitis B virus (HBV), human papillomavirus (HPV), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and herpes simplex virus (HSV), can cause a wide range of diseases and are considered a global threat to human health. Interferon-inducible protein 16 (IFI16) binds virus DNA and triggers antiviral innate immune responses to restrict viral infection. In this study, we identified that silent information regulatory 1 (Sirtuin1, Sirt1) interacted with IFI16 and regulated IFI16-mediated innate host defense. Therefore, the activator or inhibitor of Sirt1 may have the potential to be used as a novel strategy to treat DNA virus-associated diseases. We also found that Sirt1 barely interacted with p204, the murine ortholog of human IFI16, and could not negatively regulate innate immune responses upon HSV-1 infection in mouse cells. This difference between humans and mice in the regulation of antiviral host defense might be considered in preclinical studies for antiviral treatment.