• ¹College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan 430072, China.
• ²College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan 430072, China shuh@whu.edu.cn.

IFN-γ (also known as type II IFN) is a cytokine that is critically involved in antiviral and immunomodulatory effects. IFN-γ activates JAK1 and JAK2, which lead to thephosphorylationand activation of the transcription factorSTAT1. Whether and how additional molecules are involved in the process are not fully clear. In this study, we identified parafibromin as an important componentof the IFN-γ-triggered signaling pathways. Overexpression of parafibromin promoted IFN-γ-triggered phosphorylation ofSTAT1at Tyr(701), subsequent expression of downstream genes, and cellular antiviral response, whereas knockdown of parafibrominhad opposite effects.Parafibromin interacted withJAK1/2, promoted the interactions ofJAK1-JAK2 andJAK1/2-STAT1, and promoted tyrosine phosphorylation of STAT1 by JAKs after IFN-γ stimulation. Our results reveal a previously uncharacterized role of parafibromin in mediating IFN-γ-triggered signaling and cellular effects.