Small heterodimer partner (SHP) is an orphan nuclear receptor that acts as transcriptional co-repressor by interacting with a diverse set of other nuclear receptors and transcription factors. Creb binding partner (CBP) is situated on nucleus and serves as transcription co-activator. Against viral infection, several viral sensors recognize the viral nucleic acid. In downstream of those signals, CBP interacts with transcription factors and binds on enhancer region upstream of the IFN-β transcription start site in mammalian DNA. Making IFN-β enhancesome, subsequent IFN-β protein is inducted and expression of IFN-β is regulated. During acute infection, we confirmed that SHP was translocated to nucleus and bound with CBP clearly. Using Bone Marrow-Derived Macrophage and alveolar macrophage of SHP knock-out mice and SHP knock-down stable cell lines, we could also check that loss of SHP enhance IFN-β cytokine secretion against VSV, PR8, Poly(I:C), 5’ppp-dsRNA, HSV and Poly(dA:dT). Thus, SHP might be involved in innate immunity, and can reduce the immune reaction. [The National Research Foundation of Korea (Grant no. 2015020957)]