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Viruses 2016, 8(5), 146; doi:10.3390/v8050146

HACE1 Negatively Regulates Virus-Triggered Type I IFN Signaling by Impeding the Formation of the MAVS-TRAF3 Complex

Key Laboratory of Medical Immunology (National Health and Family Planning Commission of China), Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
These authors contributed equally.
*
Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 27 January 2016 / Revised: 3 May 2016 / Accepted: 17 May 2016 / Published: 21 May 2016
(This article belongs to the Section Antivirals & Vaccines)
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Abstract

During virus infection, the cascade signaling pathway that leads to the production of proinflammatory cytokines is controlled at multiple levels to avoid detrimental overreaction. HACE1 has been characterized as an important tumor suppressor. Here, we identified HACE1 as an important negative regulator of virus-triggered type I IFN signaling. Overexpression of HACE1 inhibited Sendai virus- or poly (I:C)-induced signaling and resulted in reduced IFNB1 production and enhanced virus replication. Knockdown of HACE1 expression exhibited the opposite effects. Ubiquitin E3 ligase activity of the dead mutant HACE1/C876A had a comparable inhibitory function as WT HACE1, suggesting that the suppressive function of HACE1 on virus-induced signaling is independent of its E3 ligase activity. Further study indicated that HACE1 acted downstream of MAVS and upstream of TBK1. Mechanistic studies showed that HACE1 exerts its inhibitory role on virus-induced signaling by disrupting the MAVS-TRAF3 complex. Therefore, we uncovered a novel function of HACE1 in innate immunity regulation. View Full-Text
Keywords: HACE1; TRAF3; MAVS; interferon; inflammation HACE1; TRAF3; MAVS; interferon; inflammation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Mao, H.-T.; Wang, Y.; Cai, J.; Meng, J.-L.; Zhou, Y.; Pan, Y.; Qian, X.-P.; Zhang, Y.; Zhang, J. HACE1 Negatively Regulates Virus-Triggered Type I IFN Signaling by Impeding the Formation of the MAVS-TRAF3 Complex. Viruses 2016, 8, 146.

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