SAMHD1 suppresses innate immune responses to viral infections and inflammatory stimuli by inhibiting the NF-κB and interferon pathways

Significance Although the host protein SAMHD1 has been studied as a restriction factor to inhibit retroviral infection, it is unknown whether and how SAMHD1 regulates antiviral innate immune responses. Using SAMHD1 -silenced human monocytic cell lines and primary macrophages, and primary splenocytes from SAMHD1 -knockout mice, we revealed new functions and mechanisms of SAMHD1-mediated negative regulation of innate immune responses to viral infections and inflammatory stimuli. We also identified protein interactions between SAMHD1 and several key proteins in cellular signaling pathways that regulate inflammation and antiviral innate immune responses. Overall, we discovered an important role of SAMHD1 in regulating innate immune responses and defined the underlying mechanisms, which suggest that SAMHD1 might be a therapeutic target in controlling viral infections and inflammatory diseases.