Multiple truncated isoforms of MAVS prevent its spontaneous aggregation in antiviral innate immune signalling

Nan Qi, Yuheng Shi, Rui Zhang, Wenting Zhu, Bofeng Yuan, Xiaoyan Li, Changwan Wang, Xuewu Zhang, Fajian Hou

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

In response to virus infection, RIG-I-like receptors (RLRs) sense virus RNA and induce MAVS to form prion-like aggregates to further propagate antiviral signalling. Although monomeric MAVS recombinant protein can assemble into prion-like filaments spontaneously in vitro, endogenous MAVS in cells is prevented from aggregation until viral infection. The mechanism preventing cellular MAVS from spontaneous aggregation is unclear. Here we show that multiple N-terminal truncated isoforms of MAVS are essential in preventing full-length MAVS from spontaneous aggregation through transmembrane domain-mediated homotypic interaction. Without these shorter isoforms, full-length MAVS is prone to spontaneous aggregation and Nix-mediated mitophagic degradation. In the absence of N-terminally truncated forms, blocking Nix-mediated mitophagy stabilizes full-length MAVS, which aggregates spontaneously and induces the subsequent expression of type I interferon and other proinflammatory cytokines. Our data thus uncover an important mechanism preventing spontaneous aggregation of endogenous MAVS to avoid accidental activation of antiviral innate immune signalling.

Original languageEnglish (US)
Article number15676
JournalNature Communications
Volume8
DOIs
StatePublished - Jun 13 2017

Fingerprint

Nix
Prions
viruses
infectious diseases
Virus Diseases
Antiviral Agents
Protein Isoforms
Agglomeration
Mitochondrial Degradation
interferon
Virus Receptors
Interferon Type I
RNA Viruses
Recombinant Proteins
filaments
Viruses
activation
Cytokines
degradation
proteins

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Multiple truncated isoforms of MAVS prevent its spontaneous aggregation in antiviral innate immune signalling. / Qi, Nan; Shi, Yuheng; Zhang, Rui; Zhu, Wenting; Yuan, Bofeng; Li, Xiaoyan; Wang, Changwan; Zhang, Xuewu; Hou, Fajian.

In: Nature Communications, Vol. 8, 15676, 13.06.2017.

Research output: Contribution to journalArticle

Qi, Nan ; Shi, Yuheng ; Zhang, Rui ; Zhu, Wenting ; Yuan, Bofeng ; Li, Xiaoyan ; Wang, Changwan ; Zhang, Xuewu ; Hou, Fajian. / Multiple truncated isoforms of MAVS prevent its spontaneous aggregation in antiviral innate immune signalling. In: Nature Communications. 2017 ; Vol. 8.
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AU - Yuan, Bofeng

AU - Li, Xiaoyan

AU - Wang, Changwan

AU - Zhang, Xuewu

AU - Hou, Fajian

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