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Mol Cell. 2017 Oct 19;68(2):308-322.e4. doi: 10.1016/j.molcel.2017.09.005. Epub 2017 Sep 28.

Tetherin Suppresses Type I Interferon Signaling by Targeting MAVS for NDP52-Mediated Selective Autophagic Degradation in Human Cells.

Author information

1
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510275, China.
2
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510275, China; Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510006, China. Electronic address: cuij5@mail.sysu.edu.cn.

Abstract

Tetherin (BST2/CD317) is an interferon-inducible antiviral factor known for its ability to block the release of enveloped viruses from infected cells. Yet its role in type I interferon (IFN) signaling remains poorly defined. Here, we demonstrate that Tetherin is a negative regulator of RIG-I like receptor (RLR)-mediated type I IFN signaling by targeting MAVS. The induction of Tetherin by type I IFN accelerates MAVS degradation via ubiquitin-dependent selective autophagy in human cells. Moreover, Tetherin recruits E3 ubiquitin ligase MARCH8 to catalyze K27-linked ubiquitin chains on MAVS at lysine 7, which serves as a recognition signal for NDP52-dependent autophagic degradation. Taken together, our findings reveal a negative feedback loop of RLR signaling generated by Tetherin-MARCH8-MAVS-NDP52 axis and provide insights into a better understanding of the crosstalk between selective autophagy and optimal deactivation of type I IFN signaling.

KEYWORDS:

K27-linked ubiquitination; MARCH8; MAVS; NDP52; Tetherin; selective autophagy; type I interferon

PMID:
28965816
DOI:
10.1016/j.molcel.2017.09.005
[Indexed for MEDLINE]
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