Human HAUS8 (non-phospho Ser 19/20) blocking peptide

Mitochondrial anti-viral signaling protein (VISA), additionally termed MAVS, IPS-1 and Cardif, is located at the outer membrane of mitochondria and is an essential adaptor in the Rig-like receptor (RLRs) signaling pathway. Upon viral infection, activated RLRs interact with VISA on mitochondria, forming a RLR-VISA platform, leading to the recruitment of different TRAF family members, including TRAF3, TRAF2 and TRAF6. This results in the phosphorylation and nuclear translocation of interferon regulatory factors 3 and 7 (IRF3/IRF7) by TANK binding kinase 1 (TBK1) and/or IKK epsilon, as well as activation of NF-B, to induce type I interferons (IFNs) and pro-inflammatory cytokines. It remains to be elucidated how VISA functions as a scaffold for protein complex assembly in mitochondria to regulate RLR-VISA antiviral signaling. In the present study, it was demonstrated that HAUS augmin like complex subunit 8 (HAUS8) augments the RLR-VISA-dependent antiviral signaling pathway by targeting the VISA complex. Co-immunoprecipitation verified that HAUS8 was associated with VISA and the VISA signaling complex components retinoic acid-inducible gene I (RIG-I) and TBK1 when the RLR-VISA signaling pathway was activated. The data demonstrated that overexpression of HAUS8 significantly promoted the activity of the transcription factors NF-B, IRF3 and the IFN- promoter induced by Sendai virus-mediated RLR-VISA signaling. HAUS8 increased the polyubiquitination of VISA, RIG-I and TBK1. Knockdown of HAUS8 inhibited the activation of the transcription factors IRF-3, NF-B and the IFN- promoter triggered by Sendai virus. Collectively, these results demonstrated that HAUS8 may function as a positive regulator of RLR-VISA dependent antiviral signaling by targeting the VISA complex, providing a novel regulatory mechanism of antiviral responses.