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Article

HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA

  • Authors:
    • Tian‑Sheng He
    • Tian Chen
    • Dan‑Dan Wang
    • Liang‑Guo Xu
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Functional Small Organic Molecules, Ministry of Education and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, P.R. China
  • Pages: 2458-2466
    |
    Published online on: June 15, 2018
       https://doi.org/10.3892/mmr.2018.9171
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Abstract

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 IKKε, as well as activation of NF‑κB, 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‑κB, IRF3 and the IFN‑β 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‑κB and the IFN‑β 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.
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Copy and paste a formatted citation
Spandidos Publications style
He TS, Chen T, Wang DD and Xu LG: HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA. Mol Med Rep 18: 2458-2466, 2018.
APA
He, T., Chen, T., Wang, D., & Xu, L. (2018). HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA. Molecular Medicine Reports, 18, 2458-2466. https://doi.org/10.3892/mmr.2018.9171
MLA
He, T., Chen, T., Wang, D., Xu, L."HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA". Molecular Medicine Reports 18.2 (2018): 2458-2466.
Chicago
He, T., Chen, T., Wang, D., Xu, L."HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA". Molecular Medicine Reports 18, no. 2 (2018): 2458-2466. https://doi.org/10.3892/mmr.2018.9171
Copy and paste a formatted citation
x
Spandidos Publications style
He TS, Chen T, Wang DD and Xu LG: HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA. Mol Med Rep 18: 2458-2466, 2018.
APA
He, T., Chen, T., Wang, D., & Xu, L. (2018). HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA. Molecular Medicine Reports, 18, 2458-2466. https://doi.org/10.3892/mmr.2018.9171
MLA
He, T., Chen, T., Wang, D., Xu, L."HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA". Molecular Medicine Reports 18.2 (2018): 2458-2466.
Chicago
He, T., Chen, T., Wang, D., Xu, L."HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA". Molecular Medicine Reports 18, no. 2 (2018): 2458-2466. https://doi.org/10.3892/mmr.2018.9171
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