Activation of TLR signaling is a first line of the host defense system in the elimination of invading pathogens.1 Insulin-like growth factor binding protein, acid-labile subunit (IGFALS) is a leucine-rich glycoprotein. By prolonging the half-life of IGF-I in the vascular system,2 IGFALS regulates the bioavailability of IGF, which is crucial for normal growth and development and metabolic regulation.3,4 However, the role of IGFALS in antiviral innate immune responses has not been established. In this study, we found that IGFALS is virus inducible, while it in turn inhibits viral replication. Mechanistically, IGFALS directly associates with IRAK1 and TRAF6, facilitating IRAK1/TRAF6 complex formation and enhancing K63-linked polyubiquitination of both proteins for full activation, thereby facilitating antiviral signaling.
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